Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells
The role of cellular metabolism in regulating cell proliferation and differentiation remains poorly understood. For example, most mammalian cells cannot proliferate without exogenous glutamine supplementation even though glutamine is a non-essential amino acid. Here we show that mouse embryonic stem...
Ausführliche Beschreibung
Autor*in: |
Carey, Bryce W [verfasserIn] |
---|
Format: |
Artikel |
---|---|
Sprache: |
Englisch |
Erschienen: |
2015 |
---|
Übergeordnetes Werk: |
Enthalten in: Nature - London : Macmillan Publishers Limited, part of Springer Nature, 1869, 518(2015), 7539, Seite 413-416 |
---|---|
Übergeordnetes Werk: |
volume:518 ; year:2015 ; number:7539 ; pages:413-416 |
Links: |
---|
DOI / URN: |
10.1038/nature13981 |
---|
Katalog-ID: |
OLC1962477436 |
---|
LEADER | 01000caa a2200265 4500 | ||
---|---|---|---|
001 | OLC1962477436 | ||
003 | DE-627 | ||
005 | 20230714155557.0 | ||
007 | tu | ||
008 | 160206s2015 xx ||||| 00| ||eng c | ||
024 | 7 | |a 10.1038/nature13981 |2 doi | |
028 | 5 | 2 | |a PQ20160617 |
035 | |a (DE-627)OLC1962477436 | ||
035 | |a (DE-599)GBVOLC1962477436 | ||
035 | |a (PRQ)c2469-864c492511d3471090375de41ce2046bac55ce942e423bb3f992f55ee980f3240 | ||
035 | |a (KEY)0072945020150000518753900413intracellularketoglutaratemaintainsthepluripotency | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
082 | 0 | 4 | |a 070 |a 500 |q DNB |
082 | 0 | 4 | |a 500 |q AVZ |
084 | |a BIODIV |2 fid | ||
100 | 1 | |a Carey, Bryce W |e verfasserin |4 aut | |
245 | 1 | 0 | |a Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells |
264 | 1 | |c 2015 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
338 | |a Band |b nc |2 rdacarrier | ||
520 | |a The role of cellular metabolism in regulating cell proliferation and differentiation remains poorly understood. For example, most mammalian cells cannot proliferate without exogenous glutamine supplementation even though glutamine is a non-essential amino acid. Here we show that mouse embryonic stem (ES) cells grown under conditions that maintain naive pluripotency are capable of proliferation in the absence of exogenous glutamine. Despite this, ES cells consume high levels of exogenous glutamine when the metabolite is available. In comparison to more differentiated cells, naive ES cells utilize both glucose and glutamine catabolism to maintain a high level of intracellular α-ketoglutarate (αKG). Consequently, naive ES cells exhibit an elevated αKG to succinate ratio that promotes histone/DNA demethylation and maintains pluripotency. Direct manipulation of the intracellular αKG/succinate ratio is sufficient to regulate multiple chromatin modifications, including H3K27me3 and ten-eleven translocation (Tet)-dependent DNA demethylation, which contribute to the regulation of pluripotency-associated gene expression. In vitro, supplementation with cell-permeable αKG directly supports ES-cell self-renewal while cell-permeable succinate promotes differentiation. This work reveals that intracellular αKG/succinate levels can contribute to the maintenance of cellular identity and have a mechanistic role in the transcriptional and epigenetic state of stem cells. | ||
650 | 4 | |a Histones - metabolism | |
650 | 4 | |a Embryonic Stem Cells - metabolism | |
650 | 4 | |a Transcription, Genetic - drug effects | |
650 | 4 | |a Intracellular Space - metabolism | |
650 | 4 | |a Embryonic Stem Cells - drug effects | |
650 | 4 | |a Embryonic Stem Cells - cytology | |
650 | 4 | |a DNA Methylation - drug effects | |
650 | 4 | |a Succinic Acid - metabolism | |
650 | 4 | |a Epigenesis, Genetic - genetics | |
650 | 4 | |a Pluripotent Stem Cells - metabolism | |
650 | 4 | |a Pluripotent Stem Cells - drug effects | |
650 | 4 | |a Ketoglutaric Acids - metabolism | |
650 | 4 | |a Chromatin - drug effects | |
650 | 4 | |a Ketoglutaric Acids - pharmacology | |
650 | 4 | |a Glutamic Acid - metabolism | |
650 | 4 | |a Cell Differentiation - drug effects | |
650 | 4 | |a Pluripotent Stem Cells - cytology | |
650 | 4 | |a Succinic Acid - pharmacology | |
650 | 4 | |a Glucose - metabolism | |
650 | 4 | |a Epigenesis, Genetic - drug effects | |
700 | 1 | |a Finley, Lydia W S |4 oth | |
700 | 1 | |a Cross, Justin R |4 oth | |
700 | 1 | |a Allis, C David |4 oth | |
700 | 1 | |a Thompson, Craig B |4 oth | |
773 | 0 | 8 | |i Enthalten in |t Nature |d London : Macmillan Publishers Limited, part of Springer Nature, 1869 |g 518(2015), 7539, Seite 413-416 |w (DE-627)129292834 |w (DE-600)120714-3 |w (DE-576)014473941 |x 0028-0836 |7 nnns |
773 | 1 | 8 | |g volume:518 |g year:2015 |g number:7539 |g pages:413-416 |
856 | 4 | 1 | |u http://dx.doi.org/10.1038/nature13981 |3 Volltext |
856 | 4 | 2 | |u http://www.ncbi.nlm.nih.gov/pubmed/25487152 |
856 | 4 | 2 | |u http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4336218&tool=pmcentrez&rendertype=abstract |
912 | |a GBV_USEFLAG_A | ||
912 | |a SYSFLAG_A | ||
912 | |a GBV_OLC | ||
912 | |a FID-BIODIV | ||
912 | |a SSG-OLC-PHY | ||
912 | |a SSG-OLC-CHE | ||
912 | |a SSG-OLC-MAT | ||
912 | |a SSG-OLC-FOR | ||
912 | |a SSG-OLC-SPO | ||
912 | |a SSG-OLC-PHA | ||
912 | |a SSG-OLC-DE-84 | ||
912 | |a SSG-OPC-FOR | ||
912 | |a GBV_ILN_11 | ||
912 | |a GBV_ILN_21 | ||
912 | |a GBV_ILN_22 | ||
912 | |a GBV_ILN_30 | ||
912 | |a GBV_ILN_40 | ||
912 | |a GBV_ILN_47 | ||
912 | |a GBV_ILN_55 | ||
912 | |a GBV_ILN_59 | ||
912 | |a GBV_ILN_60 | ||
912 | |a GBV_ILN_62 | ||
912 | |a GBV_ILN_69 | ||
912 | |a GBV_ILN_70 | ||
912 | |a GBV_ILN_73 | ||
912 | |a GBV_ILN_100 | ||
912 | |a GBV_ILN_101 | ||
912 | |a GBV_ILN_110 | ||
912 | |a GBV_ILN_120 | ||
912 | |a GBV_ILN_154 | ||
912 | |a GBV_ILN_160 | ||
912 | |a GBV_ILN_168 | ||
912 | |a GBV_ILN_170 | ||
912 | |a GBV_ILN_171 | ||
912 | |a GBV_ILN_211 | ||
912 | |a GBV_ILN_267 | ||
912 | |a GBV_ILN_290 | ||
912 | |a GBV_ILN_294 | ||
912 | |a GBV_ILN_601 | ||
912 | |a GBV_ILN_647 | ||
912 | |a GBV_ILN_754 | ||
912 | |a GBV_ILN_2001 | ||
912 | |a GBV_ILN_2002 | ||
912 | |a GBV_ILN_2003 | ||
912 | |a GBV_ILN_2005 | ||
912 | |a GBV_ILN_2007 | ||
912 | |a GBV_ILN_2008 | ||
912 | |a GBV_ILN_2015 | ||
912 | |a GBV_ILN_2016 | ||
912 | |a GBV_ILN_2018 | ||
912 | |a GBV_ILN_2020 | ||
912 | |a GBV_ILN_2026 | ||
912 | |a GBV_ILN_2095 | ||
912 | |a GBV_ILN_2116 | ||
912 | |a GBV_ILN_2120 | ||
912 | |a GBV_ILN_2121 | ||
912 | |a GBV_ILN_2173 | ||
912 | |a GBV_ILN_2219 | ||
912 | |a GBV_ILN_2221 | ||
912 | |a GBV_ILN_2279 | ||
912 | |a GBV_ILN_2286 | ||
912 | |a GBV_ILN_4012 | ||
912 | |a GBV_ILN_4035 | ||
912 | |a GBV_ILN_4046 | ||
912 | |a GBV_ILN_4125 | ||
912 | |a GBV_ILN_4219 | ||
912 | |a GBV_ILN_4251 | ||
912 | |a GBV_ILN_4277 | ||
912 | |a GBV_ILN_4302 | ||
912 | |a GBV_ILN_4305 | ||
912 | |a GBV_ILN_4306 | ||
912 | |a GBV_ILN_4313 | ||
912 | |a GBV_ILN_4314 | ||
912 | |a GBV_ILN_4317 | ||
912 | |a GBV_ILN_4320 | ||
912 | |a GBV_ILN_4324 | ||
912 | |a GBV_ILN_4700 | ||
951 | |a AR | ||
952 | |d 518 |j 2015 |e 7539 |h 413-416 |
author_variant |
b w c bw bwc |
---|---|
matchkey_str |
article:00280836:2015----::nrcluaktguaaeanantelrptny |
hierarchy_sort_str |
2015 |
publishDate |
2015 |
allfields |
10.1038/nature13981 doi PQ20160617 (DE-627)OLC1962477436 (DE-599)GBVOLC1962477436 (PRQ)c2469-864c492511d3471090375de41ce2046bac55ce942e423bb3f992f55ee980f3240 (KEY)0072945020150000518753900413intracellularketoglutaratemaintainsthepluripotency DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid Carey, Bryce W verfasserin aut Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The role of cellular metabolism in regulating cell proliferation and differentiation remains poorly understood. For example, most mammalian cells cannot proliferate without exogenous glutamine supplementation even though glutamine is a non-essential amino acid. Here we show that mouse embryonic stem (ES) cells grown under conditions that maintain naive pluripotency are capable of proliferation in the absence of exogenous glutamine. Despite this, ES cells consume high levels of exogenous glutamine when the metabolite is available. In comparison to more differentiated cells, naive ES cells utilize both glucose and glutamine catabolism to maintain a high level of intracellular α-ketoglutarate (αKG). Consequently, naive ES cells exhibit an elevated αKG to succinate ratio that promotes histone/DNA demethylation and maintains pluripotency. Direct manipulation of the intracellular αKG/succinate ratio is sufficient to regulate multiple chromatin modifications, including H3K27me3 and ten-eleven translocation (Tet)-dependent DNA demethylation, which contribute to the regulation of pluripotency-associated gene expression. In vitro, supplementation with cell-permeable αKG directly supports ES-cell self-renewal while cell-permeable succinate promotes differentiation. This work reveals that intracellular αKG/succinate levels can contribute to the maintenance of cellular identity and have a mechanistic role in the transcriptional and epigenetic state of stem cells. Histones - metabolism Embryonic Stem Cells - metabolism Transcription, Genetic - drug effects Intracellular Space - metabolism Embryonic Stem Cells - drug effects Embryonic Stem Cells - cytology DNA Methylation - drug effects Succinic Acid - metabolism Epigenesis, Genetic - genetics Pluripotent Stem Cells - metabolism Pluripotent Stem Cells - drug effects Ketoglutaric Acids - metabolism Chromatin - drug effects Ketoglutaric Acids - pharmacology Glutamic Acid - metabolism Cell Differentiation - drug effects Pluripotent Stem Cells - cytology Succinic Acid - pharmacology Glucose - metabolism Epigenesis, Genetic - drug effects Finley, Lydia W S oth Cross, Justin R oth Allis, C David oth Thompson, Craig B oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 518(2015), 7539, Seite 413-416 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:518 year:2015 number:7539 pages:413-416 http://dx.doi.org/10.1038/nature13981 Volltext http://www.ncbi.nlm.nih.gov/pubmed/25487152 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4336218&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 518 2015 7539 413-416 |
spelling |
10.1038/nature13981 doi PQ20160617 (DE-627)OLC1962477436 (DE-599)GBVOLC1962477436 (PRQ)c2469-864c492511d3471090375de41ce2046bac55ce942e423bb3f992f55ee980f3240 (KEY)0072945020150000518753900413intracellularketoglutaratemaintainsthepluripotency DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid Carey, Bryce W verfasserin aut Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The role of cellular metabolism in regulating cell proliferation and differentiation remains poorly understood. For example, most mammalian cells cannot proliferate without exogenous glutamine supplementation even though glutamine is a non-essential amino acid. Here we show that mouse embryonic stem (ES) cells grown under conditions that maintain naive pluripotency are capable of proliferation in the absence of exogenous glutamine. Despite this, ES cells consume high levels of exogenous glutamine when the metabolite is available. In comparison to more differentiated cells, naive ES cells utilize both glucose and glutamine catabolism to maintain a high level of intracellular α-ketoglutarate (αKG). Consequently, naive ES cells exhibit an elevated αKG to succinate ratio that promotes histone/DNA demethylation and maintains pluripotency. Direct manipulation of the intracellular αKG/succinate ratio is sufficient to regulate multiple chromatin modifications, including H3K27me3 and ten-eleven translocation (Tet)-dependent DNA demethylation, which contribute to the regulation of pluripotency-associated gene expression. In vitro, supplementation with cell-permeable αKG directly supports ES-cell self-renewal while cell-permeable succinate promotes differentiation. This work reveals that intracellular αKG/succinate levels can contribute to the maintenance of cellular identity and have a mechanistic role in the transcriptional and epigenetic state of stem cells. Histones - metabolism Embryonic Stem Cells - metabolism Transcription, Genetic - drug effects Intracellular Space - metabolism Embryonic Stem Cells - drug effects Embryonic Stem Cells - cytology DNA Methylation - drug effects Succinic Acid - metabolism Epigenesis, Genetic - genetics Pluripotent Stem Cells - metabolism Pluripotent Stem Cells - drug effects Ketoglutaric Acids - metabolism Chromatin - drug effects Ketoglutaric Acids - pharmacology Glutamic Acid - metabolism Cell Differentiation - drug effects Pluripotent Stem Cells - cytology Succinic Acid - pharmacology Glucose - metabolism Epigenesis, Genetic - drug effects Finley, Lydia W S oth Cross, Justin R oth Allis, C David oth Thompson, Craig B oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 518(2015), 7539, Seite 413-416 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:518 year:2015 number:7539 pages:413-416 http://dx.doi.org/10.1038/nature13981 Volltext http://www.ncbi.nlm.nih.gov/pubmed/25487152 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4336218&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 518 2015 7539 413-416 |
allfields_unstemmed |
10.1038/nature13981 doi PQ20160617 (DE-627)OLC1962477436 (DE-599)GBVOLC1962477436 (PRQ)c2469-864c492511d3471090375de41ce2046bac55ce942e423bb3f992f55ee980f3240 (KEY)0072945020150000518753900413intracellularketoglutaratemaintainsthepluripotency DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid Carey, Bryce W verfasserin aut Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The role of cellular metabolism in regulating cell proliferation and differentiation remains poorly understood. For example, most mammalian cells cannot proliferate without exogenous glutamine supplementation even though glutamine is a non-essential amino acid. Here we show that mouse embryonic stem (ES) cells grown under conditions that maintain naive pluripotency are capable of proliferation in the absence of exogenous glutamine. Despite this, ES cells consume high levels of exogenous glutamine when the metabolite is available. In comparison to more differentiated cells, naive ES cells utilize both glucose and glutamine catabolism to maintain a high level of intracellular α-ketoglutarate (αKG). Consequently, naive ES cells exhibit an elevated αKG to succinate ratio that promotes histone/DNA demethylation and maintains pluripotency. Direct manipulation of the intracellular αKG/succinate ratio is sufficient to regulate multiple chromatin modifications, including H3K27me3 and ten-eleven translocation (Tet)-dependent DNA demethylation, which contribute to the regulation of pluripotency-associated gene expression. In vitro, supplementation with cell-permeable αKG directly supports ES-cell self-renewal while cell-permeable succinate promotes differentiation. This work reveals that intracellular αKG/succinate levels can contribute to the maintenance of cellular identity and have a mechanistic role in the transcriptional and epigenetic state of stem cells. Histones - metabolism Embryonic Stem Cells - metabolism Transcription, Genetic - drug effects Intracellular Space - metabolism Embryonic Stem Cells - drug effects Embryonic Stem Cells - cytology DNA Methylation - drug effects Succinic Acid - metabolism Epigenesis, Genetic - genetics Pluripotent Stem Cells - metabolism Pluripotent Stem Cells - drug effects Ketoglutaric Acids - metabolism Chromatin - drug effects Ketoglutaric Acids - pharmacology Glutamic Acid - metabolism Cell Differentiation - drug effects Pluripotent Stem Cells - cytology Succinic Acid - pharmacology Glucose - metabolism Epigenesis, Genetic - drug effects Finley, Lydia W S oth Cross, Justin R oth Allis, C David oth Thompson, Craig B oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 518(2015), 7539, Seite 413-416 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:518 year:2015 number:7539 pages:413-416 http://dx.doi.org/10.1038/nature13981 Volltext http://www.ncbi.nlm.nih.gov/pubmed/25487152 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4336218&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 518 2015 7539 413-416 |
allfieldsGer |
10.1038/nature13981 doi PQ20160617 (DE-627)OLC1962477436 (DE-599)GBVOLC1962477436 (PRQ)c2469-864c492511d3471090375de41ce2046bac55ce942e423bb3f992f55ee980f3240 (KEY)0072945020150000518753900413intracellularketoglutaratemaintainsthepluripotency DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid Carey, Bryce W verfasserin aut Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The role of cellular metabolism in regulating cell proliferation and differentiation remains poorly understood. For example, most mammalian cells cannot proliferate without exogenous glutamine supplementation even though glutamine is a non-essential amino acid. Here we show that mouse embryonic stem (ES) cells grown under conditions that maintain naive pluripotency are capable of proliferation in the absence of exogenous glutamine. Despite this, ES cells consume high levels of exogenous glutamine when the metabolite is available. In comparison to more differentiated cells, naive ES cells utilize both glucose and glutamine catabolism to maintain a high level of intracellular α-ketoglutarate (αKG). Consequently, naive ES cells exhibit an elevated αKG to succinate ratio that promotes histone/DNA demethylation and maintains pluripotency. Direct manipulation of the intracellular αKG/succinate ratio is sufficient to regulate multiple chromatin modifications, including H3K27me3 and ten-eleven translocation (Tet)-dependent DNA demethylation, which contribute to the regulation of pluripotency-associated gene expression. In vitro, supplementation with cell-permeable αKG directly supports ES-cell self-renewal while cell-permeable succinate promotes differentiation. This work reveals that intracellular αKG/succinate levels can contribute to the maintenance of cellular identity and have a mechanistic role in the transcriptional and epigenetic state of stem cells. Histones - metabolism Embryonic Stem Cells - metabolism Transcription, Genetic - drug effects Intracellular Space - metabolism Embryonic Stem Cells - drug effects Embryonic Stem Cells - cytology DNA Methylation - drug effects Succinic Acid - metabolism Epigenesis, Genetic - genetics Pluripotent Stem Cells - metabolism Pluripotent Stem Cells - drug effects Ketoglutaric Acids - metabolism Chromatin - drug effects Ketoglutaric Acids - pharmacology Glutamic Acid - metabolism Cell Differentiation - drug effects Pluripotent Stem Cells - cytology Succinic Acid - pharmacology Glucose - metabolism Epigenesis, Genetic - drug effects Finley, Lydia W S oth Cross, Justin R oth Allis, C David oth Thompson, Craig B oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 518(2015), 7539, Seite 413-416 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:518 year:2015 number:7539 pages:413-416 http://dx.doi.org/10.1038/nature13981 Volltext http://www.ncbi.nlm.nih.gov/pubmed/25487152 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4336218&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 518 2015 7539 413-416 |
allfieldsSound |
10.1038/nature13981 doi PQ20160617 (DE-627)OLC1962477436 (DE-599)GBVOLC1962477436 (PRQ)c2469-864c492511d3471090375de41ce2046bac55ce942e423bb3f992f55ee980f3240 (KEY)0072945020150000518753900413intracellularketoglutaratemaintainsthepluripotency DE-627 ger DE-627 rakwb eng 070 500 DNB 500 AVZ BIODIV fid Carey, Bryce W verfasserin aut Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The role of cellular metabolism in regulating cell proliferation and differentiation remains poorly understood. For example, most mammalian cells cannot proliferate without exogenous glutamine supplementation even though glutamine is a non-essential amino acid. Here we show that mouse embryonic stem (ES) cells grown under conditions that maintain naive pluripotency are capable of proliferation in the absence of exogenous glutamine. Despite this, ES cells consume high levels of exogenous glutamine when the metabolite is available. In comparison to more differentiated cells, naive ES cells utilize both glucose and glutamine catabolism to maintain a high level of intracellular α-ketoglutarate (αKG). Consequently, naive ES cells exhibit an elevated αKG to succinate ratio that promotes histone/DNA demethylation and maintains pluripotency. Direct manipulation of the intracellular αKG/succinate ratio is sufficient to regulate multiple chromatin modifications, including H3K27me3 and ten-eleven translocation (Tet)-dependent DNA demethylation, which contribute to the regulation of pluripotency-associated gene expression. In vitro, supplementation with cell-permeable αKG directly supports ES-cell self-renewal while cell-permeable succinate promotes differentiation. This work reveals that intracellular αKG/succinate levels can contribute to the maintenance of cellular identity and have a mechanistic role in the transcriptional and epigenetic state of stem cells. Histones - metabolism Embryonic Stem Cells - metabolism Transcription, Genetic - drug effects Intracellular Space - metabolism Embryonic Stem Cells - drug effects Embryonic Stem Cells - cytology DNA Methylation - drug effects Succinic Acid - metabolism Epigenesis, Genetic - genetics Pluripotent Stem Cells - metabolism Pluripotent Stem Cells - drug effects Ketoglutaric Acids - metabolism Chromatin - drug effects Ketoglutaric Acids - pharmacology Glutamic Acid - metabolism Cell Differentiation - drug effects Pluripotent Stem Cells - cytology Succinic Acid - pharmacology Glucose - metabolism Epigenesis, Genetic - drug effects Finley, Lydia W S oth Cross, Justin R oth Allis, C David oth Thompson, Craig B oth Enthalten in Nature London : Macmillan Publishers Limited, part of Springer Nature, 1869 518(2015), 7539, Seite 413-416 (DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 0028-0836 nnns volume:518 year:2015 number:7539 pages:413-416 http://dx.doi.org/10.1038/nature13981 Volltext http://www.ncbi.nlm.nih.gov/pubmed/25487152 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4336218&tool=pmcentrez&rendertype=abstract GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 AR 518 2015 7539 413-416 |
language |
English |
source |
Enthalten in Nature 518(2015), 7539, Seite 413-416 volume:518 year:2015 number:7539 pages:413-416 |
sourceStr |
Enthalten in Nature 518(2015), 7539, Seite 413-416 volume:518 year:2015 number:7539 pages:413-416 |
format_phy_str_mv |
Article |
institution |
findex.gbv.de |
topic_facet |
Histones - metabolism Embryonic Stem Cells - metabolism Transcription, Genetic - drug effects Intracellular Space - metabolism Embryonic Stem Cells - drug effects Embryonic Stem Cells - cytology DNA Methylation - drug effects Succinic Acid - metabolism Epigenesis, Genetic - genetics Pluripotent Stem Cells - metabolism Pluripotent Stem Cells - drug effects Ketoglutaric Acids - metabolism Chromatin - drug effects Ketoglutaric Acids - pharmacology Glutamic Acid - metabolism Cell Differentiation - drug effects Pluripotent Stem Cells - cytology Succinic Acid - pharmacology Glucose - metabolism Epigenesis, Genetic - drug effects |
dewey-raw |
070 |
isfreeaccess_bool |
false |
container_title |
Nature |
authorswithroles_txt_mv |
Carey, Bryce W @@aut@@ Finley, Lydia W S @@oth@@ Cross, Justin R @@oth@@ Allis, C David @@oth@@ Thompson, Craig B @@oth@@ |
publishDateDaySort_date |
2015-01-01T00:00:00Z |
hierarchy_top_id |
129292834 |
dewey-sort |
270 |
id |
OLC1962477436 |
language_de |
englisch |
fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">OLC1962477436</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230714155557.0</controlfield><controlfield tag="007">tu</controlfield><controlfield tag="008">160206s2015 xx ||||| 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1038/nature13981</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">PQ20160617</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)OLC1962477436</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)GBVOLC1962477436</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(PRQ)c2469-864c492511d3471090375de41ce2046bac55ce942e423bb3f992f55ee980f3240</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(KEY)0072945020150000518753900413intracellularketoglutaratemaintainsthepluripotency</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">070</subfield><subfield code="a">500</subfield><subfield code="q">DNB</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">500</subfield><subfield code="q">AVZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">BIODIV</subfield><subfield code="2">fid</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Carey, Bryce W</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2015</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">ohne Hilfsmittel zu benutzen</subfield><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Band</subfield><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">The role of cellular metabolism in regulating cell proliferation and differentiation remains poorly understood. For example, most mammalian cells cannot proliferate without exogenous glutamine supplementation even though glutamine is a non-essential amino acid. Here we show that mouse embryonic stem (ES) cells grown under conditions that maintain naive pluripotency are capable of proliferation in the absence of exogenous glutamine. Despite this, ES cells consume high levels of exogenous glutamine when the metabolite is available. In comparison to more differentiated cells, naive ES cells utilize both glucose and glutamine catabolism to maintain a high level of intracellular α-ketoglutarate (αKG). Consequently, naive ES cells exhibit an elevated αKG to succinate ratio that promotes histone/DNA demethylation and maintains pluripotency. Direct manipulation of the intracellular αKG/succinate ratio is sufficient to regulate multiple chromatin modifications, including H3K27me3 and ten-eleven translocation (Tet)-dependent DNA demethylation, which contribute to the regulation of pluripotency-associated gene expression. In vitro, supplementation with cell-permeable αKG directly supports ES-cell self-renewal while cell-permeable succinate promotes differentiation. This work reveals that intracellular αKG/succinate levels can contribute to the maintenance of cellular identity and have a mechanistic role in the transcriptional and epigenetic state of stem cells.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Histones - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Embryonic Stem Cells - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Transcription, Genetic - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Intracellular Space - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Embryonic Stem Cells - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Embryonic Stem Cells - cytology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA Methylation - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Succinic Acid - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Epigenesis, Genetic - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pluripotent Stem Cells - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pluripotent Stem Cells - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Ketoglutaric Acids - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Chromatin - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Ketoglutaric Acids - pharmacology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Glutamic Acid - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Cell Differentiation - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pluripotent Stem Cells - cytology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Succinic Acid - pharmacology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Glucose - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Epigenesis, Genetic - drug effects</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Finley, Lydia W S</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Cross, Justin R</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Allis, C David</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Thompson, Craig B</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Nature</subfield><subfield code="d">London : Macmillan Publishers Limited, part of Springer Nature, 1869</subfield><subfield code="g">518(2015), 7539, Seite 413-416</subfield><subfield code="w">(DE-627)129292834</subfield><subfield code="w">(DE-600)120714-3</subfield><subfield code="w">(DE-576)014473941</subfield><subfield code="x">0028-0836</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:518</subfield><subfield code="g">year:2015</subfield><subfield code="g">number:7539</subfield><subfield code="g">pages:413-416</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">http://dx.doi.org/10.1038/nature13981</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://www.ncbi.nlm.nih.gov/pubmed/25487152</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4336218&tool=pmcentrez&rendertype=abstract</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_OLC</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-BIODIV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHY</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-CHE</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-SPO</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-DE-84</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_21</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_30</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_47</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_55</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_59</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_100</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_101</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_120</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_154</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_160</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_168</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_171</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_211</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_267</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_290</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_294</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_601</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_647</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_754</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2001</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2002</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2007</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2008</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2015</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2016</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2018</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2020</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2026</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2095</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2116</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2120</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2121</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2173</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2219</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2221</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2279</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2286</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4035</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4046</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4219</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4251</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4277</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4302</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4314</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4317</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4320</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">518</subfield><subfield code="j">2015</subfield><subfield code="e">7539</subfield><subfield code="h">413-416</subfield></datafield></record></collection>
|
author |
Carey, Bryce W |
spellingShingle |
Carey, Bryce W ddc 070 ddc 500 fid BIODIV misc Histones - metabolism misc Embryonic Stem Cells - metabolism misc Transcription, Genetic - drug effects misc Intracellular Space - metabolism misc Embryonic Stem Cells - drug effects misc Embryonic Stem Cells - cytology misc DNA Methylation - drug effects misc Succinic Acid - metabolism misc Epigenesis, Genetic - genetics misc Pluripotent Stem Cells - metabolism misc Pluripotent Stem Cells - drug effects misc Ketoglutaric Acids - metabolism misc Chromatin - drug effects misc Ketoglutaric Acids - pharmacology misc Glutamic Acid - metabolism misc Cell Differentiation - drug effects misc Pluripotent Stem Cells - cytology misc Succinic Acid - pharmacology misc Glucose - metabolism misc Epigenesis, Genetic - drug effects Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells |
authorStr |
Carey, Bryce W |
ppnlink_with_tag_str_mv |
@@773@@(DE-627)129292834 |
format |
Article |
dewey-ones |
070 - News media, journalism & publishing 500 - Natural sciences & mathematics |
delete_txt_mv |
keep |
author_role |
aut |
collection |
OLC |
remote_str |
false |
illustrated |
Not Illustrated |
issn |
0028-0836 |
topic_title |
070 500 DNB 500 AVZ BIODIV fid Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells Histones - metabolism Embryonic Stem Cells - metabolism Transcription, Genetic - drug effects Intracellular Space - metabolism Embryonic Stem Cells - drug effects Embryonic Stem Cells - cytology DNA Methylation - drug effects Succinic Acid - metabolism Epigenesis, Genetic - genetics Pluripotent Stem Cells - metabolism Pluripotent Stem Cells - drug effects Ketoglutaric Acids - metabolism Chromatin - drug effects Ketoglutaric Acids - pharmacology Glutamic Acid - metabolism Cell Differentiation - drug effects Pluripotent Stem Cells - cytology Succinic Acid - pharmacology Glucose - metabolism Epigenesis, Genetic - drug effects |
topic |
ddc 070 ddc 500 fid BIODIV misc Histones - metabolism misc Embryonic Stem Cells - metabolism misc Transcription, Genetic - drug effects misc Intracellular Space - metabolism misc Embryonic Stem Cells - drug effects misc Embryonic Stem Cells - cytology misc DNA Methylation - drug effects misc Succinic Acid - metabolism misc Epigenesis, Genetic - genetics misc Pluripotent Stem Cells - metabolism misc Pluripotent Stem Cells - drug effects misc Ketoglutaric Acids - metabolism misc Chromatin - drug effects misc Ketoglutaric Acids - pharmacology misc Glutamic Acid - metabolism misc Cell Differentiation - drug effects misc Pluripotent Stem Cells - cytology misc Succinic Acid - pharmacology misc Glucose - metabolism misc Epigenesis, Genetic - drug effects |
topic_unstemmed |
ddc 070 ddc 500 fid BIODIV misc Histones - metabolism misc Embryonic Stem Cells - metabolism misc Transcription, Genetic - drug effects misc Intracellular Space - metabolism misc Embryonic Stem Cells - drug effects misc Embryonic Stem Cells - cytology misc DNA Methylation - drug effects misc Succinic Acid - metabolism misc Epigenesis, Genetic - genetics misc Pluripotent Stem Cells - metabolism misc Pluripotent Stem Cells - drug effects misc Ketoglutaric Acids - metabolism misc Chromatin - drug effects misc Ketoglutaric Acids - pharmacology misc Glutamic Acid - metabolism misc Cell Differentiation - drug effects misc Pluripotent Stem Cells - cytology misc Succinic Acid - pharmacology misc Glucose - metabolism misc Epigenesis, Genetic - drug effects |
topic_browse |
ddc 070 ddc 500 fid BIODIV misc Histones - metabolism misc Embryonic Stem Cells - metabolism misc Transcription, Genetic - drug effects misc Intracellular Space - metabolism misc Embryonic Stem Cells - drug effects misc Embryonic Stem Cells - cytology misc DNA Methylation - drug effects misc Succinic Acid - metabolism misc Epigenesis, Genetic - genetics misc Pluripotent Stem Cells - metabolism misc Pluripotent Stem Cells - drug effects misc Ketoglutaric Acids - metabolism misc Chromatin - drug effects misc Ketoglutaric Acids - pharmacology misc Glutamic Acid - metabolism misc Cell Differentiation - drug effects misc Pluripotent Stem Cells - cytology misc Succinic Acid - pharmacology misc Glucose - metabolism misc Epigenesis, Genetic - drug effects |
format_facet |
Aufsätze Gedruckte Aufsätze |
format_main_str_mv |
Text Zeitschrift/Artikel |
carriertype_str_mv |
nc |
author2_variant |
l w s f lws lwsf j r c jr jrc c d a cd cda c b t cb cbt |
hierarchy_parent_title |
Nature |
hierarchy_parent_id |
129292834 |
dewey-tens |
070 - News media, journalism & publishing 500 - Science |
hierarchy_top_title |
Nature |
isfreeaccess_txt |
false |
familylinks_str_mv |
(DE-627)129292834 (DE-600)120714-3 (DE-576)014473941 |
title |
Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells |
ctrlnum |
(DE-627)OLC1962477436 (DE-599)GBVOLC1962477436 (PRQ)c2469-864c492511d3471090375de41ce2046bac55ce942e423bb3f992f55ee980f3240 (KEY)0072945020150000518753900413intracellularketoglutaratemaintainsthepluripotency |
title_full |
Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells |
author_sort |
Carey, Bryce W |
journal |
Nature |
journalStr |
Nature |
lang_code |
eng |
isOA_bool |
false |
dewey-hundreds |
000 - Computer science, information & general works 500 - Science |
recordtype |
marc |
publishDateSort |
2015 |
contenttype_str_mv |
txt |
container_start_page |
413 |
author_browse |
Carey, Bryce W |
container_volume |
518 |
class |
070 500 DNB 500 AVZ BIODIV fid |
format_se |
Aufsätze |
author-letter |
Carey, Bryce W |
doi_str_mv |
10.1038/nature13981 |
dewey-full |
070 500 |
title_sort |
intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells |
title_auth |
Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells |
abstract |
The role of cellular metabolism in regulating cell proliferation and differentiation remains poorly understood. For example, most mammalian cells cannot proliferate without exogenous glutamine supplementation even though glutamine is a non-essential amino acid. Here we show that mouse embryonic stem (ES) cells grown under conditions that maintain naive pluripotency are capable of proliferation in the absence of exogenous glutamine. Despite this, ES cells consume high levels of exogenous glutamine when the metabolite is available. In comparison to more differentiated cells, naive ES cells utilize both glucose and glutamine catabolism to maintain a high level of intracellular α-ketoglutarate (αKG). Consequently, naive ES cells exhibit an elevated αKG to succinate ratio that promotes histone/DNA demethylation and maintains pluripotency. Direct manipulation of the intracellular αKG/succinate ratio is sufficient to regulate multiple chromatin modifications, including H3K27me3 and ten-eleven translocation (Tet)-dependent DNA demethylation, which contribute to the regulation of pluripotency-associated gene expression. In vitro, supplementation with cell-permeable αKG directly supports ES-cell self-renewal while cell-permeable succinate promotes differentiation. This work reveals that intracellular αKG/succinate levels can contribute to the maintenance of cellular identity and have a mechanistic role in the transcriptional and epigenetic state of stem cells. |
abstractGer |
The role of cellular metabolism in regulating cell proliferation and differentiation remains poorly understood. For example, most mammalian cells cannot proliferate without exogenous glutamine supplementation even though glutamine is a non-essential amino acid. Here we show that mouse embryonic stem (ES) cells grown under conditions that maintain naive pluripotency are capable of proliferation in the absence of exogenous glutamine. Despite this, ES cells consume high levels of exogenous glutamine when the metabolite is available. In comparison to more differentiated cells, naive ES cells utilize both glucose and glutamine catabolism to maintain a high level of intracellular α-ketoglutarate (αKG). Consequently, naive ES cells exhibit an elevated αKG to succinate ratio that promotes histone/DNA demethylation and maintains pluripotency. Direct manipulation of the intracellular αKG/succinate ratio is sufficient to regulate multiple chromatin modifications, including H3K27me3 and ten-eleven translocation (Tet)-dependent DNA demethylation, which contribute to the regulation of pluripotency-associated gene expression. In vitro, supplementation with cell-permeable αKG directly supports ES-cell self-renewal while cell-permeable succinate promotes differentiation. This work reveals that intracellular αKG/succinate levels can contribute to the maintenance of cellular identity and have a mechanistic role in the transcriptional and epigenetic state of stem cells. |
abstract_unstemmed |
The role of cellular metabolism in regulating cell proliferation and differentiation remains poorly understood. For example, most mammalian cells cannot proliferate without exogenous glutamine supplementation even though glutamine is a non-essential amino acid. Here we show that mouse embryonic stem (ES) cells grown under conditions that maintain naive pluripotency are capable of proliferation in the absence of exogenous glutamine. Despite this, ES cells consume high levels of exogenous glutamine when the metabolite is available. In comparison to more differentiated cells, naive ES cells utilize both glucose and glutamine catabolism to maintain a high level of intracellular α-ketoglutarate (αKG). Consequently, naive ES cells exhibit an elevated αKG to succinate ratio that promotes histone/DNA demethylation and maintains pluripotency. Direct manipulation of the intracellular αKG/succinate ratio is sufficient to regulate multiple chromatin modifications, including H3K27me3 and ten-eleven translocation (Tet)-dependent DNA demethylation, which contribute to the regulation of pluripotency-associated gene expression. In vitro, supplementation with cell-permeable αKG directly supports ES-cell self-renewal while cell-permeable succinate promotes differentiation. This work reveals that intracellular αKG/succinate levels can contribute to the maintenance of cellular identity and have a mechanistic role in the transcriptional and epigenetic state of stem cells. |
collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-SPO SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-FOR GBV_ILN_11 GBV_ILN_21 GBV_ILN_22 GBV_ILN_30 GBV_ILN_40 GBV_ILN_47 GBV_ILN_55 GBV_ILN_59 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_100 GBV_ILN_101 GBV_ILN_110 GBV_ILN_120 GBV_ILN_154 GBV_ILN_160 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_267 GBV_ILN_290 GBV_ILN_294 GBV_ILN_601 GBV_ILN_647 GBV_ILN_754 GBV_ILN_2001 GBV_ILN_2002 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2015 GBV_ILN_2016 GBV_ILN_2018 GBV_ILN_2020 GBV_ILN_2026 GBV_ILN_2095 GBV_ILN_2116 GBV_ILN_2120 GBV_ILN_2121 GBV_ILN_2173 GBV_ILN_2219 GBV_ILN_2221 GBV_ILN_2279 GBV_ILN_2286 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4046 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4302 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4317 GBV_ILN_4320 GBV_ILN_4324 GBV_ILN_4700 |
container_issue |
7539 |
title_short |
Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells |
url |
http://dx.doi.org/10.1038/nature13981 http://www.ncbi.nlm.nih.gov/pubmed/25487152 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4336218&tool=pmcentrez&rendertype=abstract |
remote_bool |
false |
author2 |
Finley, Lydia W S Cross, Justin R Allis, C David Thompson, Craig B |
author2Str |
Finley, Lydia W S Cross, Justin R Allis, C David Thompson, Craig B |
ppnlink |
129292834 |
mediatype_str_mv |
n |
isOA_txt |
false |
hochschulschrift_bool |
false |
author2_role |
oth oth oth oth |
doi_str |
10.1038/nature13981 |
up_date |
2024-07-04T03:40:29.036Z |
_version_ |
1803618278741901312 |
fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">OLC1962477436</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230714155557.0</controlfield><controlfield tag="007">tu</controlfield><controlfield tag="008">160206s2015 xx ||||| 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1038/nature13981</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">PQ20160617</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)OLC1962477436</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)GBVOLC1962477436</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(PRQ)c2469-864c492511d3471090375de41ce2046bac55ce942e423bb3f992f55ee980f3240</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(KEY)0072945020150000518753900413intracellularketoglutaratemaintainsthepluripotency</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">070</subfield><subfield code="a">500</subfield><subfield code="q">DNB</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">500</subfield><subfield code="q">AVZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">BIODIV</subfield><subfield code="2">fid</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Carey, Bryce W</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2015</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">ohne Hilfsmittel zu benutzen</subfield><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Band</subfield><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">The role of cellular metabolism in regulating cell proliferation and differentiation remains poorly understood. For example, most mammalian cells cannot proliferate without exogenous glutamine supplementation even though glutamine is a non-essential amino acid. Here we show that mouse embryonic stem (ES) cells grown under conditions that maintain naive pluripotency are capable of proliferation in the absence of exogenous glutamine. Despite this, ES cells consume high levels of exogenous glutamine when the metabolite is available. In comparison to more differentiated cells, naive ES cells utilize both glucose and glutamine catabolism to maintain a high level of intracellular α-ketoglutarate (αKG). Consequently, naive ES cells exhibit an elevated αKG to succinate ratio that promotes histone/DNA demethylation and maintains pluripotency. Direct manipulation of the intracellular αKG/succinate ratio is sufficient to regulate multiple chromatin modifications, including H3K27me3 and ten-eleven translocation (Tet)-dependent DNA demethylation, which contribute to the regulation of pluripotency-associated gene expression. In vitro, supplementation with cell-permeable αKG directly supports ES-cell self-renewal while cell-permeable succinate promotes differentiation. This work reveals that intracellular αKG/succinate levels can contribute to the maintenance of cellular identity and have a mechanistic role in the transcriptional and epigenetic state of stem cells.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Histones - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Embryonic Stem Cells - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Transcription, Genetic - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Intracellular Space - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Embryonic Stem Cells - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Embryonic Stem Cells - cytology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA Methylation - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Succinic Acid - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Epigenesis, Genetic - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pluripotent Stem Cells - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pluripotent Stem Cells - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Ketoglutaric Acids - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Chromatin - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Ketoglutaric Acids - pharmacology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Glutamic Acid - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Cell Differentiation - drug effects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pluripotent Stem Cells - cytology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Succinic Acid - pharmacology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Glucose - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Epigenesis, Genetic - drug effects</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Finley, Lydia W S</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Cross, Justin R</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Allis, C David</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Thompson, Craig B</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Nature</subfield><subfield code="d">London : Macmillan Publishers Limited, part of Springer Nature, 1869</subfield><subfield code="g">518(2015), 7539, Seite 413-416</subfield><subfield code="w">(DE-627)129292834</subfield><subfield code="w">(DE-600)120714-3</subfield><subfield code="w">(DE-576)014473941</subfield><subfield code="x">0028-0836</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:518</subfield><subfield code="g">year:2015</subfield><subfield code="g">number:7539</subfield><subfield code="g">pages:413-416</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">http://dx.doi.org/10.1038/nature13981</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://www.ncbi.nlm.nih.gov/pubmed/25487152</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4336218&tool=pmcentrez&rendertype=abstract</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_OLC</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">FID-BIODIV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHY</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-CHE</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-MAT</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-SPO</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-DE-84</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OPC-FOR</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_21</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_30</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_47</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_55</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_59</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_100</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_101</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_120</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_154</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_160</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_168</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_171</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_211</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_267</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_290</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_294</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_601</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_647</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_754</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2001</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2002</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2007</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2008</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2015</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2016</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2018</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2020</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2026</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2095</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2116</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2120</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2121</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2173</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2219</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2221</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2279</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2286</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4035</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4046</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4219</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4251</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4277</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4302</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4314</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4317</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4320</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">518</subfield><subfield code="j">2015</subfield><subfield code="e">7539</subfield><subfield code="h">413-416</subfield></datafield></record></collection>
|
score |
7.402128 |