The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency
Background Pluripotency is proposed to exist in two different stages: Naive and Primed. Conventional human pluripotent cells are essentially in the primed stage. In recent years, several protocols have claimed to generate naive human embryonic stem cells (hESCs). To the best of our knowledge, none o...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Yousefi, Meisam [verfasserIn] Marashi, Sayed-Amir [verfasserIn] Sharifi-Zarchi, Ali [verfasserIn] Taleahmad, Sara [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2019 |
|---|
| Schlagwörter: |
|---|
| Übergeordnetes Werk: |
Enthalten in: Cell & bioscience - London : BioMed Central, 2011, 9(2019), 1 vom: 29. Aug. |
|---|---|
| Übergeordnetes Werk: |
volume:9 ; year:2019 ; number:1 ; day:29 ; month:08 |
| Links: |
|---|
| DOI / URN: |
10.1186/s13578-019-0334-7 |
|---|
| Katalog-ID: |
SPR031856470 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | SPR031856470 | ||
| 003 | DE-627 | ||
| 005 | 20220111194208.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 201007s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s13578-019-0334-7 |2 doi | |
| 035 | |a (DE-627)SPR031856470 | ||
| 035 | |a (SPR)s13578-019-0334-7-e | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 050 |q ASE |
| 100 | 1 | |a Yousefi, Meisam |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Background Pluripotency is proposed to exist in two different stages: Naive and Primed. Conventional human pluripotent cells are essentially in the primed stage. In recent years, several protocols have claimed to generate naive human embryonic stem cells (hESCs). To the best of our knowledge, none of these protocols is currently recognized as the gold standard method. Furthermore, the consistency of the resulting cells from these diverse protocols at the molecular level is yet to be shown. Additionally, little is known about the principles that govern the metabolic differences between naive and primed pluripotency. In this work, using a computational approach, we tried to shed light on these basic issues. Results We showed that, after batch effect removal, the transcriptome data of eight different protocols which supposedly produce naive hESCs are clustered consistently when compared to the primed ones. Next, by integrating transcriptomes of all hESCs obtained by these protocols, we reconstructed p-hESCNet and n-hESCNet, the first metabolic network models representing hESCs. By exploiting reporter metabolite analysis we showed that the status of NAD%$^{+}%$ and the metabolites involved in the TCA cycle are significantly altered between naive and primed hESCs. Furthermore, using flux variability analysis (FVA), the models showed that the kynurenine-mediated metabolism of tryptophan is remarkably downregulated in naive human pluripotent cells. Conclusion The aim of the present paper is twofold. Firstly, our findings confirm the applicability of all these protocols for generating naive hESCs, due to their consistency at the transcriptome level. Secondly, we showed that in silico metabolic models of hESCs can be used to simulate the metabolic states of naive and primed pluripotency. Our models confirmed the OXPHOS activation in naive cells and showed that oxidation-reduction potential vary between naive and primed cells. Tryptophan metabolism is also outlined as a key pathway in primed pluripotency and the models suggest that decrements in the activity of this pathway might be an appropriate marker for naive pluripotency. | ||
| 650 | 4 | |a Systems biology |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Human embryonic stem cells |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Tryptophan metabolism |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Kynurenine metabolism |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Genome-scale metabolic networks |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Marashi, Sayed-Amir |e verfasserin |4 aut | |
| 700 | 1 | |a Sharifi-Zarchi, Ali |e verfasserin |4 aut | |
| 700 | 1 | |a Taleahmad, Sara |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell & bioscience |d London : BioMed Central, 2011 |g 9(2019), 1 vom: 29. Aug. |w (DE-627)646079387 |w (DE-600)2593367-X |x 2045-3701 |7 nnns |
| 773 | 1 | 8 | |g volume:9 |g year:2019 |g number:1 |g day:29 |g month:08 |
| 856 | 4 | 0 | |u https://dx.doi.org/10.1186/s13578-019-0334-7 |z kostenfrei |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_SPRINGER | ||
| 912 | |a GBV_ILN_11 | ||
| 912 | |a GBV_ILN_20 | ||
| 912 | |a GBV_ILN_22 | ||
| 912 | |a GBV_ILN_23 | ||
| 912 | |a GBV_ILN_24 | ||
| 912 | |a GBV_ILN_31 | ||
| 912 | |a GBV_ILN_39 | ||
| 912 | |a GBV_ILN_40 | ||
| 912 | |a GBV_ILN_62 | ||
| 912 | |a GBV_ILN_63 | ||
| 912 | |a GBV_ILN_65 | ||
| 912 | |a GBV_ILN_69 | ||
| 912 | |a GBV_ILN_70 | ||
| 912 | |a GBV_ILN_73 | ||
| 912 | |a GBV_ILN_95 | ||
| 912 | |a GBV_ILN_105 | ||
| 912 | |a GBV_ILN_110 | ||
| 912 | |a GBV_ILN_151 | ||
| 912 | |a GBV_ILN_161 | ||
| 912 | |a GBV_ILN_213 | ||
| 912 | |a GBV_ILN_230 | ||
| 912 | |a GBV_ILN_285 | ||
| 912 | |a GBV_ILN_293 | ||
| 912 | |a GBV_ILN_370 | ||
| 912 | |a GBV_ILN_602 | ||
| 912 | |a GBV_ILN_2003 | ||
| 912 | |a GBV_ILN_2005 | ||
| 912 | |a GBV_ILN_2009 | ||
| 912 | |a GBV_ILN_2014 | ||
| 912 | |a GBV_ILN_2055 | ||
| 912 | |a GBV_ILN_2111 | ||
| 912 | |a GBV_ILN_4012 | ||
| 912 | |a GBV_ILN_4037 | ||
| 912 | |a GBV_ILN_4112 | ||
| 912 | |a GBV_ILN_4125 | ||
| 912 | |a GBV_ILN_4126 | ||
| 912 | |a GBV_ILN_4249 | ||
| 912 | |a GBV_ILN_4305 | ||
| 912 | |a GBV_ILN_4306 | ||
| 912 | |a GBV_ILN_4307 | ||
| 912 | |a GBV_ILN_4313 | ||
| 912 | |a GBV_ILN_4322 | ||
| 912 | |a GBV_ILN_4323 | ||
| 912 | |a GBV_ILN_4324 | ||
| 912 | |a GBV_ILN_4325 | ||
| 912 | |a GBV_ILN_4338 | ||
| 912 | |a GBV_ILN_4367 | ||
| 912 | |a GBV_ILN_4700 | ||
| 951 | |a AR | ||
| 952 | |d 9 |j 2019 |e 1 |b 29 |c 08 | ||
| author_variant |
m y my s a m sam a s z asz s t st |
|---|---|
| matchkey_str |
article:20453701:2019----::hmtblcewrmdlfrmdavhmnmroiseclsnelnshipracooiaineutoptniln |
| hierarchy_sort_str |
2019 |
| publishDate |
2019 |
| allfields |
10.1186/s13578-019-0334-7 doi (DE-627)SPR031856470 (SPR)s13578-019-0334-7-e DE-627 ger DE-627 rakwb eng 050 ASE Yousefi, Meisam verfasserin aut The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Pluripotency is proposed to exist in two different stages: Naive and Primed. Conventional human pluripotent cells are essentially in the primed stage. In recent years, several protocols have claimed to generate naive human embryonic stem cells (hESCs). To the best of our knowledge, none of these protocols is currently recognized as the gold standard method. Furthermore, the consistency of the resulting cells from these diverse protocols at the molecular level is yet to be shown. Additionally, little is known about the principles that govern the metabolic differences between naive and primed pluripotency. In this work, using a computational approach, we tried to shed light on these basic issues. Results We showed that, after batch effect removal, the transcriptome data of eight different protocols which supposedly produce naive hESCs are clustered consistently when compared to the primed ones. Next, by integrating transcriptomes of all hESCs obtained by these protocols, we reconstructed p-hESCNet and n-hESCNet, the first metabolic network models representing hESCs. By exploiting reporter metabolite analysis we showed that the status of NAD%$^{+}%$ and the metabolites involved in the TCA cycle are significantly altered between naive and primed hESCs. Furthermore, using flux variability analysis (FVA), the models showed that the kynurenine-mediated metabolism of tryptophan is remarkably downregulated in naive human pluripotent cells. Conclusion The aim of the present paper is twofold. Firstly, our findings confirm the applicability of all these protocols for generating naive hESCs, due to their consistency at the transcriptome level. Secondly, we showed that in silico metabolic models of hESCs can be used to simulate the metabolic states of naive and primed pluripotency. Our models confirmed the OXPHOS activation in naive cells and showed that oxidation-reduction potential vary between naive and primed cells. Tryptophan metabolism is also outlined as a key pathway in primed pluripotency and the models suggest that decrements in the activity of this pathway might be an appropriate marker for naive pluripotency. Systems biology (dpeaa)DE-He213 Human embryonic stem cells (dpeaa)DE-He213 Tryptophan metabolism (dpeaa)DE-He213 Kynurenine metabolism (dpeaa)DE-He213 Genome-scale metabolic networks (dpeaa)DE-He213 Marashi, Sayed-Amir verfasserin aut Sharifi-Zarchi, Ali verfasserin aut Taleahmad, Sara verfasserin aut Enthalten in Cell & bioscience London : BioMed Central, 2011 9(2019), 1 vom: 29. Aug. (DE-627)646079387 (DE-600)2593367-X 2045-3701 nnns volume:9 year:2019 number:1 day:29 month:08 https://dx.doi.org/10.1186/s13578-019-0334-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2019 1 29 08 |
| spelling |
10.1186/s13578-019-0334-7 doi (DE-627)SPR031856470 (SPR)s13578-019-0334-7-e DE-627 ger DE-627 rakwb eng 050 ASE Yousefi, Meisam verfasserin aut The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Pluripotency is proposed to exist in two different stages: Naive and Primed. Conventional human pluripotent cells are essentially in the primed stage. In recent years, several protocols have claimed to generate naive human embryonic stem cells (hESCs). To the best of our knowledge, none of these protocols is currently recognized as the gold standard method. Furthermore, the consistency of the resulting cells from these diverse protocols at the molecular level is yet to be shown. Additionally, little is known about the principles that govern the metabolic differences between naive and primed pluripotency. In this work, using a computational approach, we tried to shed light on these basic issues. Results We showed that, after batch effect removal, the transcriptome data of eight different protocols which supposedly produce naive hESCs are clustered consistently when compared to the primed ones. Next, by integrating transcriptomes of all hESCs obtained by these protocols, we reconstructed p-hESCNet and n-hESCNet, the first metabolic network models representing hESCs. By exploiting reporter metabolite analysis we showed that the status of NAD%$^{+}%$ and the metabolites involved in the TCA cycle are significantly altered between naive and primed hESCs. Furthermore, using flux variability analysis (FVA), the models showed that the kynurenine-mediated metabolism of tryptophan is remarkably downregulated in naive human pluripotent cells. Conclusion The aim of the present paper is twofold. Firstly, our findings confirm the applicability of all these protocols for generating naive hESCs, due to their consistency at the transcriptome level. Secondly, we showed that in silico metabolic models of hESCs can be used to simulate the metabolic states of naive and primed pluripotency. Our models confirmed the OXPHOS activation in naive cells and showed that oxidation-reduction potential vary between naive and primed cells. Tryptophan metabolism is also outlined as a key pathway in primed pluripotency and the models suggest that decrements in the activity of this pathway might be an appropriate marker for naive pluripotency. Systems biology (dpeaa)DE-He213 Human embryonic stem cells (dpeaa)DE-He213 Tryptophan metabolism (dpeaa)DE-He213 Kynurenine metabolism (dpeaa)DE-He213 Genome-scale metabolic networks (dpeaa)DE-He213 Marashi, Sayed-Amir verfasserin aut Sharifi-Zarchi, Ali verfasserin aut Taleahmad, Sara verfasserin aut Enthalten in Cell & bioscience London : BioMed Central, 2011 9(2019), 1 vom: 29. Aug. (DE-627)646079387 (DE-600)2593367-X 2045-3701 nnns volume:9 year:2019 number:1 day:29 month:08 https://dx.doi.org/10.1186/s13578-019-0334-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2019 1 29 08 |
| allfields_unstemmed |
10.1186/s13578-019-0334-7 doi (DE-627)SPR031856470 (SPR)s13578-019-0334-7-e DE-627 ger DE-627 rakwb eng 050 ASE Yousefi, Meisam verfasserin aut The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Pluripotency is proposed to exist in two different stages: Naive and Primed. Conventional human pluripotent cells are essentially in the primed stage. In recent years, several protocols have claimed to generate naive human embryonic stem cells (hESCs). To the best of our knowledge, none of these protocols is currently recognized as the gold standard method. Furthermore, the consistency of the resulting cells from these diverse protocols at the molecular level is yet to be shown. Additionally, little is known about the principles that govern the metabolic differences between naive and primed pluripotency. In this work, using a computational approach, we tried to shed light on these basic issues. Results We showed that, after batch effect removal, the transcriptome data of eight different protocols which supposedly produce naive hESCs are clustered consistently when compared to the primed ones. Next, by integrating transcriptomes of all hESCs obtained by these protocols, we reconstructed p-hESCNet and n-hESCNet, the first metabolic network models representing hESCs. By exploiting reporter metabolite analysis we showed that the status of NAD%$^{+}%$ and the metabolites involved in the TCA cycle are significantly altered between naive and primed hESCs. Furthermore, using flux variability analysis (FVA), the models showed that the kynurenine-mediated metabolism of tryptophan is remarkably downregulated in naive human pluripotent cells. Conclusion The aim of the present paper is twofold. Firstly, our findings confirm the applicability of all these protocols for generating naive hESCs, due to their consistency at the transcriptome level. Secondly, we showed that in silico metabolic models of hESCs can be used to simulate the metabolic states of naive and primed pluripotency. Our models confirmed the OXPHOS activation in naive cells and showed that oxidation-reduction potential vary between naive and primed cells. Tryptophan metabolism is also outlined as a key pathway in primed pluripotency and the models suggest that decrements in the activity of this pathway might be an appropriate marker for naive pluripotency. Systems biology (dpeaa)DE-He213 Human embryonic stem cells (dpeaa)DE-He213 Tryptophan metabolism (dpeaa)DE-He213 Kynurenine metabolism (dpeaa)DE-He213 Genome-scale metabolic networks (dpeaa)DE-He213 Marashi, Sayed-Amir verfasserin aut Sharifi-Zarchi, Ali verfasserin aut Taleahmad, Sara verfasserin aut Enthalten in Cell & bioscience London : BioMed Central, 2011 9(2019), 1 vom: 29. Aug. (DE-627)646079387 (DE-600)2593367-X 2045-3701 nnns volume:9 year:2019 number:1 day:29 month:08 https://dx.doi.org/10.1186/s13578-019-0334-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2019 1 29 08 |
| allfieldsGer |
10.1186/s13578-019-0334-7 doi (DE-627)SPR031856470 (SPR)s13578-019-0334-7-e DE-627 ger DE-627 rakwb eng 050 ASE Yousefi, Meisam verfasserin aut The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Pluripotency is proposed to exist in two different stages: Naive and Primed. Conventional human pluripotent cells are essentially in the primed stage. In recent years, several protocols have claimed to generate naive human embryonic stem cells (hESCs). To the best of our knowledge, none of these protocols is currently recognized as the gold standard method. Furthermore, the consistency of the resulting cells from these diverse protocols at the molecular level is yet to be shown. Additionally, little is known about the principles that govern the metabolic differences between naive and primed pluripotency. In this work, using a computational approach, we tried to shed light on these basic issues. Results We showed that, after batch effect removal, the transcriptome data of eight different protocols which supposedly produce naive hESCs are clustered consistently when compared to the primed ones. Next, by integrating transcriptomes of all hESCs obtained by these protocols, we reconstructed p-hESCNet and n-hESCNet, the first metabolic network models representing hESCs. By exploiting reporter metabolite analysis we showed that the status of NAD%$^{+}%$ and the metabolites involved in the TCA cycle are significantly altered between naive and primed hESCs. Furthermore, using flux variability analysis (FVA), the models showed that the kynurenine-mediated metabolism of tryptophan is remarkably downregulated in naive human pluripotent cells. Conclusion The aim of the present paper is twofold. Firstly, our findings confirm the applicability of all these protocols for generating naive hESCs, due to their consistency at the transcriptome level. Secondly, we showed that in silico metabolic models of hESCs can be used to simulate the metabolic states of naive and primed pluripotency. Our models confirmed the OXPHOS activation in naive cells and showed that oxidation-reduction potential vary between naive and primed cells. Tryptophan metabolism is also outlined as a key pathway in primed pluripotency and the models suggest that decrements in the activity of this pathway might be an appropriate marker for naive pluripotency. Systems biology (dpeaa)DE-He213 Human embryonic stem cells (dpeaa)DE-He213 Tryptophan metabolism (dpeaa)DE-He213 Kynurenine metabolism (dpeaa)DE-He213 Genome-scale metabolic networks (dpeaa)DE-He213 Marashi, Sayed-Amir verfasserin aut Sharifi-Zarchi, Ali verfasserin aut Taleahmad, Sara verfasserin aut Enthalten in Cell & bioscience London : BioMed Central, 2011 9(2019), 1 vom: 29. Aug. (DE-627)646079387 (DE-600)2593367-X 2045-3701 nnns volume:9 year:2019 number:1 day:29 month:08 https://dx.doi.org/10.1186/s13578-019-0334-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2019 1 29 08 |
| allfieldsSound |
10.1186/s13578-019-0334-7 doi (DE-627)SPR031856470 (SPR)s13578-019-0334-7-e DE-627 ger DE-627 rakwb eng 050 ASE Yousefi, Meisam verfasserin aut The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Pluripotency is proposed to exist in two different stages: Naive and Primed. Conventional human pluripotent cells are essentially in the primed stage. In recent years, several protocols have claimed to generate naive human embryonic stem cells (hESCs). To the best of our knowledge, none of these protocols is currently recognized as the gold standard method. Furthermore, the consistency of the resulting cells from these diverse protocols at the molecular level is yet to be shown. Additionally, little is known about the principles that govern the metabolic differences between naive and primed pluripotency. In this work, using a computational approach, we tried to shed light on these basic issues. Results We showed that, after batch effect removal, the transcriptome data of eight different protocols which supposedly produce naive hESCs are clustered consistently when compared to the primed ones. Next, by integrating transcriptomes of all hESCs obtained by these protocols, we reconstructed p-hESCNet and n-hESCNet, the first metabolic network models representing hESCs. By exploiting reporter metabolite analysis we showed that the status of NAD%$^{+}%$ and the metabolites involved in the TCA cycle are significantly altered between naive and primed hESCs. Furthermore, using flux variability analysis (FVA), the models showed that the kynurenine-mediated metabolism of tryptophan is remarkably downregulated in naive human pluripotent cells. Conclusion The aim of the present paper is twofold. Firstly, our findings confirm the applicability of all these protocols for generating naive hESCs, due to their consistency at the transcriptome level. Secondly, we showed that in silico metabolic models of hESCs can be used to simulate the metabolic states of naive and primed pluripotency. Our models confirmed the OXPHOS activation in naive cells and showed that oxidation-reduction potential vary between naive and primed cells. Tryptophan metabolism is also outlined as a key pathway in primed pluripotency and the models suggest that decrements in the activity of this pathway might be an appropriate marker for naive pluripotency. Systems biology (dpeaa)DE-He213 Human embryonic stem cells (dpeaa)DE-He213 Tryptophan metabolism (dpeaa)DE-He213 Kynurenine metabolism (dpeaa)DE-He213 Genome-scale metabolic networks (dpeaa)DE-He213 Marashi, Sayed-Amir verfasserin aut Sharifi-Zarchi, Ali verfasserin aut Taleahmad, Sara verfasserin aut Enthalten in Cell & bioscience London : BioMed Central, 2011 9(2019), 1 vom: 29. Aug. (DE-627)646079387 (DE-600)2593367-X 2045-3701 nnns volume:9 year:2019 number:1 day:29 month:08 https://dx.doi.org/10.1186/s13578-019-0334-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2019 1 29 08 |
| language |
English |
| source |
Enthalten in Cell & bioscience 9(2019), 1 vom: 29. Aug. volume:9 year:2019 number:1 day:29 month:08 |
| sourceStr |
Enthalten in Cell & bioscience 9(2019), 1 vom: 29. Aug. volume:9 year:2019 number:1 day:29 month:08 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| topic_facet |
Systems biology Human embryonic stem cells Tryptophan metabolism Kynurenine metabolism Genome-scale metabolic networks |
| dewey-raw |
050 |
| isfreeaccess_bool |
true |
| container_title |
Cell & bioscience |
| authorswithroles_txt_mv |
Yousefi, Meisam @@aut@@ Marashi, Sayed-Amir @@aut@@ Sharifi-Zarchi, Ali @@aut@@ Taleahmad, Sara @@aut@@ |
| publishDateDaySort_date |
2019-08-29T00:00:00Z |
| hierarchy_top_id |
646079387 |
| dewey-sort |
250 |
| id |
SPR031856470 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR031856470</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20220111194208.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2019 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s13578-019-0334-7</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR031856470</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s13578-019-0334-7-e</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">050</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Yousefi, Meisam</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="4"><subfield code="a">The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</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">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Pluripotency is proposed to exist in two different stages: Naive and Primed. Conventional human pluripotent cells are essentially in the primed stage. In recent years, several protocols have claimed to generate naive human embryonic stem cells (hESCs). To the best of our knowledge, none of these protocols is currently recognized as the gold standard method. Furthermore, the consistency of the resulting cells from these diverse protocols at the molecular level is yet to be shown. Additionally, little is known about the principles that govern the metabolic differences between naive and primed pluripotency. In this work, using a computational approach, we tried to shed light on these basic issues. Results We showed that, after batch effect removal, the transcriptome data of eight different protocols which supposedly produce naive hESCs are clustered consistently when compared to the primed ones. Next, by integrating transcriptomes of all hESCs obtained by these protocols, we reconstructed p-hESCNet and n-hESCNet, the first metabolic network models representing hESCs. By exploiting reporter metabolite analysis we showed that the status of NAD%$^{+}%$ and the metabolites involved in the TCA cycle are significantly altered between naive and primed hESCs. Furthermore, using flux variability analysis (FVA), the models showed that the kynurenine-mediated metabolism of tryptophan is remarkably downregulated in naive human pluripotent cells. Conclusion The aim of the present paper is twofold. Firstly, our findings confirm the applicability of all these protocols for generating naive hESCs, due to their consistency at the transcriptome level. Secondly, we showed that in silico metabolic models of hESCs can be used to simulate the metabolic states of naive and primed pluripotency. Our models confirmed the OXPHOS activation in naive cells and showed that oxidation-reduction potential vary between naive and primed cells. Tryptophan metabolism is also outlined as a key pathway in primed pluripotency and the models suggest that decrements in the activity of this pathway might be an appropriate marker for naive pluripotency.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Systems biology</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Human embryonic stem cells</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tryptophan metabolism</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Kynurenine metabolism</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genome-scale metabolic networks</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Marashi, Sayed-Amir</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sharifi-Zarchi, Ali</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Taleahmad, Sara</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Cell & bioscience</subfield><subfield code="d">London : BioMed Central, 2011</subfield><subfield code="g">9(2019), 1 vom: 29. Aug.</subfield><subfield code="w">(DE-627)646079387</subfield><subfield code="w">(DE-600)2593367-X</subfield><subfield code="x">2045-3701</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:9</subfield><subfield code="g">year:2019</subfield><subfield code="g">number:1</subfield><subfield code="g">day:29</subfield><subfield code="g">month:08</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1186/s13578-019-0334-7</subfield><subfield code="z">kostenfrei</subfield><subfield code="3">Volltext</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_SPRINGER</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_20</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_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</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_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</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_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</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_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_370</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</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_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</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_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</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_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</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_4307</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_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</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_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</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">9</subfield><subfield code="j">2019</subfield><subfield code="e">1</subfield><subfield code="b">29</subfield><subfield code="c">08</subfield></datafield></record></collection>
|
| author |
Yousefi, Meisam |
| spellingShingle |
Yousefi, Meisam ddc 050 misc Systems biology misc Human embryonic stem cells misc Tryptophan metabolism misc Kynurenine metabolism misc Genome-scale metabolic networks The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency |
| authorStr |
Yousefi, Meisam |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)646079387 |
| format |
electronic Article |
| dewey-ones |
050 - General serial publications |
| delete_txt_mv |
keep |
| author_role |
aut aut aut aut |
| collection |
springer |
| remote_str |
true |
| illustrated |
Not Illustrated |
| issn |
2045-3701 |
| topic_title |
050 ASE The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency Systems biology (dpeaa)DE-He213 Human embryonic stem cells (dpeaa)DE-He213 Tryptophan metabolism (dpeaa)DE-He213 Kynurenine metabolism (dpeaa)DE-He213 Genome-scale metabolic networks (dpeaa)DE-He213 |
| topic |
ddc 050 misc Systems biology misc Human embryonic stem cells misc Tryptophan metabolism misc Kynurenine metabolism misc Genome-scale metabolic networks |
| topic_unstemmed |
ddc 050 misc Systems biology misc Human embryonic stem cells misc Tryptophan metabolism misc Kynurenine metabolism misc Genome-scale metabolic networks |
| topic_browse |
ddc 050 misc Systems biology misc Human embryonic stem cells misc Tryptophan metabolism misc Kynurenine metabolism misc Genome-scale metabolic networks |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
cr |
| hierarchy_parent_title |
Cell & bioscience |
| hierarchy_parent_id |
646079387 |
| dewey-tens |
050 - Magazines, journals & serials |
| hierarchy_top_title |
Cell & bioscience |
| isfreeaccess_txt |
true |
| familylinks_str_mv |
(DE-627)646079387 (DE-600)2593367-X |
| title |
The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency |
| ctrlnum |
(DE-627)SPR031856470 (SPR)s13578-019-0334-7-e |
| title_full |
The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency |
| author_sort |
Yousefi, Meisam |
| journal |
Cell & bioscience |
| journalStr |
Cell & bioscience |
| lang_code |
eng |
| isOA_bool |
true |
| dewey-hundreds |
000 - Computer science, information & general works |
| recordtype |
marc |
| publishDateSort |
2019 |
| contenttype_str_mv |
txt |
| author_browse |
Yousefi, Meisam Marashi, Sayed-Amir Sharifi-Zarchi, Ali Taleahmad, Sara |
| container_volume |
9 |
| class |
050 ASE |
| format_se |
Elektronische Aufsätze |
| author-letter |
Yousefi, Meisam |
| doi_str_mv |
10.1186/s13578-019-0334-7 |
| dewey-full |
050 |
| author2-role |
verfasserin |
| title_sort |
metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency |
| title_auth |
The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency |
| abstract |
Background Pluripotency is proposed to exist in two different stages: Naive and Primed. Conventional human pluripotent cells are essentially in the primed stage. In recent years, several protocols have claimed to generate naive human embryonic stem cells (hESCs). To the best of our knowledge, none of these protocols is currently recognized as the gold standard method. Furthermore, the consistency of the resulting cells from these diverse protocols at the molecular level is yet to be shown. Additionally, little is known about the principles that govern the metabolic differences between naive and primed pluripotency. In this work, using a computational approach, we tried to shed light on these basic issues. Results We showed that, after batch effect removal, the transcriptome data of eight different protocols which supposedly produce naive hESCs are clustered consistently when compared to the primed ones. Next, by integrating transcriptomes of all hESCs obtained by these protocols, we reconstructed p-hESCNet and n-hESCNet, the first metabolic network models representing hESCs. By exploiting reporter metabolite analysis we showed that the status of NAD%$^{+}%$ and the metabolites involved in the TCA cycle are significantly altered between naive and primed hESCs. Furthermore, using flux variability analysis (FVA), the models showed that the kynurenine-mediated metabolism of tryptophan is remarkably downregulated in naive human pluripotent cells. Conclusion The aim of the present paper is twofold. Firstly, our findings confirm the applicability of all these protocols for generating naive hESCs, due to their consistency at the transcriptome level. Secondly, we showed that in silico metabolic models of hESCs can be used to simulate the metabolic states of naive and primed pluripotency. Our models confirmed the OXPHOS activation in naive cells and showed that oxidation-reduction potential vary between naive and primed cells. Tryptophan metabolism is also outlined as a key pathway in primed pluripotency and the models suggest that decrements in the activity of this pathway might be an appropriate marker for naive pluripotency. |
| abstractGer |
Background Pluripotency is proposed to exist in two different stages: Naive and Primed. Conventional human pluripotent cells are essentially in the primed stage. In recent years, several protocols have claimed to generate naive human embryonic stem cells (hESCs). To the best of our knowledge, none of these protocols is currently recognized as the gold standard method. Furthermore, the consistency of the resulting cells from these diverse protocols at the molecular level is yet to be shown. Additionally, little is known about the principles that govern the metabolic differences between naive and primed pluripotency. In this work, using a computational approach, we tried to shed light on these basic issues. Results We showed that, after batch effect removal, the transcriptome data of eight different protocols which supposedly produce naive hESCs are clustered consistently when compared to the primed ones. Next, by integrating transcriptomes of all hESCs obtained by these protocols, we reconstructed p-hESCNet and n-hESCNet, the first metabolic network models representing hESCs. By exploiting reporter metabolite analysis we showed that the status of NAD%$^{+}%$ and the metabolites involved in the TCA cycle are significantly altered between naive and primed hESCs. Furthermore, using flux variability analysis (FVA), the models showed that the kynurenine-mediated metabolism of tryptophan is remarkably downregulated in naive human pluripotent cells. Conclusion The aim of the present paper is twofold. Firstly, our findings confirm the applicability of all these protocols for generating naive hESCs, due to their consistency at the transcriptome level. Secondly, we showed that in silico metabolic models of hESCs can be used to simulate the metabolic states of naive and primed pluripotency. Our models confirmed the OXPHOS activation in naive cells and showed that oxidation-reduction potential vary between naive and primed cells. Tryptophan metabolism is also outlined as a key pathway in primed pluripotency and the models suggest that decrements in the activity of this pathway might be an appropriate marker for naive pluripotency. |
| abstract_unstemmed |
Background Pluripotency is proposed to exist in two different stages: Naive and Primed. Conventional human pluripotent cells are essentially in the primed stage. In recent years, several protocols have claimed to generate naive human embryonic stem cells (hESCs). To the best of our knowledge, none of these protocols is currently recognized as the gold standard method. Furthermore, the consistency of the resulting cells from these diverse protocols at the molecular level is yet to be shown. Additionally, little is known about the principles that govern the metabolic differences between naive and primed pluripotency. In this work, using a computational approach, we tried to shed light on these basic issues. Results We showed that, after batch effect removal, the transcriptome data of eight different protocols which supposedly produce naive hESCs are clustered consistently when compared to the primed ones. Next, by integrating transcriptomes of all hESCs obtained by these protocols, we reconstructed p-hESCNet and n-hESCNet, the first metabolic network models representing hESCs. By exploiting reporter metabolite analysis we showed that the status of NAD%$^{+}%$ and the metabolites involved in the TCA cycle are significantly altered between naive and primed hESCs. Furthermore, using flux variability analysis (FVA), the models showed that the kynurenine-mediated metabolism of tryptophan is remarkably downregulated in naive human pluripotent cells. Conclusion The aim of the present paper is twofold. Firstly, our findings confirm the applicability of all these protocols for generating naive hESCs, due to their consistency at the transcriptome level. Secondly, we showed that in silico metabolic models of hESCs can be used to simulate the metabolic states of naive and primed pluripotency. Our models confirmed the OXPHOS activation in naive cells and showed that oxidation-reduction potential vary between naive and primed cells. Tryptophan metabolism is also outlined as a key pathway in primed pluripotency and the models suggest that decrements in the activity of this pathway might be an appropriate marker for naive pluripotency. |
| collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 |
| container_issue |
1 |
| title_short |
The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency |
| url |
https://dx.doi.org/10.1186/s13578-019-0334-7 |
| remote_bool |
true |
| author2 |
Marashi, Sayed-Amir Sharifi-Zarchi, Ali Taleahmad, Sara |
| author2Str |
Marashi, Sayed-Amir Sharifi-Zarchi, Ali Taleahmad, Sara |
| ppnlink |
646079387 |
| mediatype_str_mv |
c |
| isOA_txt |
true |
| hochschulschrift_bool |
false |
| doi_str |
10.1186/s13578-019-0334-7 |
| up_date |
2024-07-04T01:32:38.648Z |
| _version_ |
1803610235758182400 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR031856470</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20220111194208.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2019 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s13578-019-0334-7</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR031856470</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s13578-019-0334-7-e</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">050</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Yousefi, Meisam</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="4"><subfield code="a">The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</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">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Pluripotency is proposed to exist in two different stages: Naive and Primed. Conventional human pluripotent cells are essentially in the primed stage. In recent years, several protocols have claimed to generate naive human embryonic stem cells (hESCs). To the best of our knowledge, none of these protocols is currently recognized as the gold standard method. Furthermore, the consistency of the resulting cells from these diverse protocols at the molecular level is yet to be shown. Additionally, little is known about the principles that govern the metabolic differences between naive and primed pluripotency. In this work, using a computational approach, we tried to shed light on these basic issues. Results We showed that, after batch effect removal, the transcriptome data of eight different protocols which supposedly produce naive hESCs are clustered consistently when compared to the primed ones. Next, by integrating transcriptomes of all hESCs obtained by these protocols, we reconstructed p-hESCNet and n-hESCNet, the first metabolic network models representing hESCs. By exploiting reporter metabolite analysis we showed that the status of NAD%$^{+}%$ and the metabolites involved in the TCA cycle are significantly altered between naive and primed hESCs. Furthermore, using flux variability analysis (FVA), the models showed that the kynurenine-mediated metabolism of tryptophan is remarkably downregulated in naive human pluripotent cells. Conclusion The aim of the present paper is twofold. Firstly, our findings confirm the applicability of all these protocols for generating naive hESCs, due to their consistency at the transcriptome level. Secondly, we showed that in silico metabolic models of hESCs can be used to simulate the metabolic states of naive and primed pluripotency. Our models confirmed the OXPHOS activation in naive cells and showed that oxidation-reduction potential vary between naive and primed cells. Tryptophan metabolism is also outlined as a key pathway in primed pluripotency and the models suggest that decrements in the activity of this pathway might be an appropriate marker for naive pluripotency.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Systems biology</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Human embryonic stem cells</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tryptophan metabolism</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Kynurenine metabolism</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genome-scale metabolic networks</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Marashi, Sayed-Amir</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sharifi-Zarchi, Ali</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Taleahmad, Sara</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Cell & bioscience</subfield><subfield code="d">London : BioMed Central, 2011</subfield><subfield code="g">9(2019), 1 vom: 29. Aug.</subfield><subfield code="w">(DE-627)646079387</subfield><subfield code="w">(DE-600)2593367-X</subfield><subfield code="x">2045-3701</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:9</subfield><subfield code="g">year:2019</subfield><subfield code="g">number:1</subfield><subfield code="g">day:29</subfield><subfield code="g">month:08</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1186/s13578-019-0334-7</subfield><subfield code="z">kostenfrei</subfield><subfield code="3">Volltext</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_SPRINGER</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_20</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_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</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_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</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_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</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_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_370</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</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_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</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_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</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_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</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_4307</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_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</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_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</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">9</subfield><subfield code="j">2019</subfield><subfield code="e">1</subfield><subfield code="b">29</subfield><subfield code="c">08</subfield></datafield></record></collection>
|
| score |
7.398033 |