Branched-chain amino acid aminotransferase-1 regulates self-renewal and pluripotency of mouse embryonic stem cells through Ras signaling

The developmental plasticity of embryonic stem cells (ESCs) is mainly controlled by well-characterized transcription factors, but additional factors, especially those related to metabolism that modulate this intrinsic program remain elusive. Here, using whole transcriptome analysis, we identified br...
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Autor*in:	Chen, Shaohui [verfasserIn] Chen, Bohan [verfasserIn] Su, Guangsong [verfasserIn] Chen, Jun [verfasserIn] Guo, Dianhao [verfasserIn] Yin, Qingqing [verfasserIn] Wang, Wenbin [verfasserIn] Zhao, Zhongfang [verfasserIn] Zhang, Lei [verfasserIn] Shi, Jiandang [verfasserIn] Lu, Wange [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	Self-renewal Pluripotency Embryonic stem cells

Übergeordnetes Werk:	Enthalten in: Stem cell research - Amsterdam [u.a.] : Elsevier, 2007, 49
Übergeordnetes Werk:	volume:49

DOI / URN:	10.1016/j.scr.2020.102097

Katalog-ID:	ELV010568093

Internformat


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245	1	0	\|a Branched-chain amino acid aminotransferase-1 regulates self-renewal and pluripotency of mouse embryonic stem cells through Ras signaling
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520			\|a The developmental plasticity of embryonic stem cells (ESCs) is mainly controlled by well-characterized transcription factors, but additional factors, especially those related to metabolism that modulate this intrinsic program remain elusive. Here, using whole transcriptome analysis, we identified branched-chain amino acid aminotransferase-1(Bcat1) as highly-expressed in mouse ESCs and dramatically down-regulated upon differentiation. Bcat1 deletion impaired pluripotency and self-renewal in mouse ESCs, while Bcat1 overexpression resulted in robust ESC self-renewal and inhibition of differentiation. Whole genome bisulfite sequencing (WGBS) analysis showed that Bcat1 deletion altered whole genome methylation levels and hence gene expression in multiple pathways. Specifically, Bcat1 deletion increased expression of RAS protein activator like 1(Rasal1), leading to inactivation of Ras-Erk/MAPK signaling, while Rasal1 inhibition rescued defects seen in Bcat1 deleted cells. In summary, we demonstrate that Bcat1 is essential for mouse ESC self-renewal and pluripotency and that this effect is mediated by DNA methylation and the Ras signaling pathway.
650		4	\|a Self-renewal
650		4	\|a Pluripotency
650		4	\|a Embryonic stem cells
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700	1		\|a Shi, Jiandang \|e verfasserin \|4 aut
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912			\|a GBV_ILN_4393
912			\|a GBV_ILN_4700
951			\|a AR
952			\|d 49

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publishDate	2020
allfields	10.1016/j.scr.2020.102097 doi (DE-627)ELV010568093 (ELSEVIER)S1873-5061(20)30398-6 DE-627 ger DE-627 rda eng 570 VZ Chen, Shaohui verfasserin aut Branched-chain amino acid aminotransferase-1 regulates self-renewal and pluripotency of mouse embryonic stem cells through Ras signaling 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The developmental plasticity of embryonic stem cells (ESCs) is mainly controlled by well-characterized transcription factors, but additional factors, especially those related to metabolism that modulate this intrinsic program remain elusive. Here, using whole transcriptome analysis, we identified branched-chain amino acid aminotransferase-1(Bcat1) as highly-expressed in mouse ESCs and dramatically down-regulated upon differentiation. Bcat1 deletion impaired pluripotency and self-renewal in mouse ESCs, while Bcat1 overexpression resulted in robust ESC self-renewal and inhibition of differentiation. Whole genome bisulfite sequencing (WGBS) analysis showed that Bcat1 deletion altered whole genome methylation levels and hence gene expression in multiple pathways. Specifically, Bcat1 deletion increased expression of RAS protein activator like 1(Rasal1), leading to inactivation of Ras-Erk/MAPK signaling, while Rasal1 inhibition rescued defects seen in Bcat1 deleted cells. In summary, we demonstrate that Bcat1 is essential for mouse ESC self-renewal and pluripotency and that this effect is mediated by DNA methylation and the Ras signaling pathway. Self-renewal Pluripotency Embryonic stem cells Chen, Bohan verfasserin aut Su, Guangsong verfasserin aut Chen, Jun verfasserin aut Guo, Dianhao verfasserin aut Yin, Qingqing verfasserin aut Wang, Wenbin verfasserin aut Zhao, Zhongfang verfasserin aut Zhang, Lei verfasserin aut Shi, Jiandang verfasserin aut Lu, Wange verfasserin aut Enthalten in Stem cell research Amsterdam [u.a.] : Elsevier, 2007 49 Online-Ressource (DE-627)548125856 (DE-600)2393143-7 (DE-576)284748463 1876-7753 nnns volume:49 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA 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_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 49
spelling	10.1016/j.scr.2020.102097 doi (DE-627)ELV010568093 (ELSEVIER)S1873-5061(20)30398-6 DE-627 ger DE-627 rda eng 570 VZ Chen, Shaohui verfasserin aut Branched-chain amino acid aminotransferase-1 regulates self-renewal and pluripotency of mouse embryonic stem cells through Ras signaling 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The developmental plasticity of embryonic stem cells (ESCs) is mainly controlled by well-characterized transcription factors, but additional factors, especially those related to metabolism that modulate this intrinsic program remain elusive. Here, using whole transcriptome analysis, we identified branched-chain amino acid aminotransferase-1(Bcat1) as highly-expressed in mouse ESCs and dramatically down-regulated upon differentiation. Bcat1 deletion impaired pluripotency and self-renewal in mouse ESCs, while Bcat1 overexpression resulted in robust ESC self-renewal and inhibition of differentiation. Whole genome bisulfite sequencing (WGBS) analysis showed that Bcat1 deletion altered whole genome methylation levels and hence gene expression in multiple pathways. Specifically, Bcat1 deletion increased expression of RAS protein activator like 1(Rasal1), leading to inactivation of Ras-Erk/MAPK signaling, while Rasal1 inhibition rescued defects seen in Bcat1 deleted cells. In summary, we demonstrate that Bcat1 is essential for mouse ESC self-renewal and pluripotency and that this effect is mediated by DNA methylation and the Ras signaling pathway. Self-renewal Pluripotency Embryonic stem cells Chen, Bohan verfasserin aut Su, Guangsong verfasserin aut Chen, Jun verfasserin aut Guo, Dianhao verfasserin aut Yin, Qingqing verfasserin aut Wang, Wenbin verfasserin aut Zhao, Zhongfang verfasserin aut Zhang, Lei verfasserin aut Shi, Jiandang verfasserin aut Lu, Wange verfasserin aut Enthalten in Stem cell research Amsterdam [u.a.] : Elsevier, 2007 49 Online-Ressource (DE-627)548125856 (DE-600)2393143-7 (DE-576)284748463 1876-7753 nnns volume:49 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA 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_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 49
allfields_unstemmed	10.1016/j.scr.2020.102097 doi (DE-627)ELV010568093 (ELSEVIER)S1873-5061(20)30398-6 DE-627 ger DE-627 rda eng 570 VZ Chen, Shaohui verfasserin aut Branched-chain amino acid aminotransferase-1 regulates self-renewal and pluripotency of mouse embryonic stem cells through Ras signaling 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The developmental plasticity of embryonic stem cells (ESCs) is mainly controlled by well-characterized transcription factors, but additional factors, especially those related to metabolism that modulate this intrinsic program remain elusive. Here, using whole transcriptome analysis, we identified branched-chain amino acid aminotransferase-1(Bcat1) as highly-expressed in mouse ESCs and dramatically down-regulated upon differentiation. Bcat1 deletion impaired pluripotency and self-renewal in mouse ESCs, while Bcat1 overexpression resulted in robust ESC self-renewal and inhibition of differentiation. Whole genome bisulfite sequencing (WGBS) analysis showed that Bcat1 deletion altered whole genome methylation levels and hence gene expression in multiple pathways. Specifically, Bcat1 deletion increased expression of RAS protein activator like 1(Rasal1), leading to inactivation of Ras-Erk/MAPK signaling, while Rasal1 inhibition rescued defects seen in Bcat1 deleted cells. In summary, we demonstrate that Bcat1 is essential for mouse ESC self-renewal and pluripotency and that this effect is mediated by DNA methylation and the Ras signaling pathway. Self-renewal Pluripotency Embryonic stem cells Chen, Bohan verfasserin aut Su, Guangsong verfasserin aut Chen, Jun verfasserin aut Guo, Dianhao verfasserin aut Yin, Qingqing verfasserin aut Wang, Wenbin verfasserin aut Zhao, Zhongfang verfasserin aut Zhang, Lei verfasserin aut Shi, Jiandang verfasserin aut Lu, Wange verfasserin aut Enthalten in Stem cell research Amsterdam [u.a.] : Elsevier, 2007 49 Online-Ressource (DE-627)548125856 (DE-600)2393143-7 (DE-576)284748463 1876-7753 nnns volume:49 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA 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_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 49
allfieldsGer	10.1016/j.scr.2020.102097 doi (DE-627)ELV010568093 (ELSEVIER)S1873-5061(20)30398-6 DE-627 ger DE-627 rda eng 570 VZ Chen, Shaohui verfasserin aut Branched-chain amino acid aminotransferase-1 regulates self-renewal and pluripotency of mouse embryonic stem cells through Ras signaling 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The developmental plasticity of embryonic stem cells (ESCs) is mainly controlled by well-characterized transcription factors, but additional factors, especially those related to metabolism that modulate this intrinsic program remain elusive. Here, using whole transcriptome analysis, we identified branched-chain amino acid aminotransferase-1(Bcat1) as highly-expressed in mouse ESCs and dramatically down-regulated upon differentiation. Bcat1 deletion impaired pluripotency and self-renewal in mouse ESCs, while Bcat1 overexpression resulted in robust ESC self-renewal and inhibition of differentiation. Whole genome bisulfite sequencing (WGBS) analysis showed that Bcat1 deletion altered whole genome methylation levels and hence gene expression in multiple pathways. Specifically, Bcat1 deletion increased expression of RAS protein activator like 1(Rasal1), leading to inactivation of Ras-Erk/MAPK signaling, while Rasal1 inhibition rescued defects seen in Bcat1 deleted cells. In summary, we demonstrate that Bcat1 is essential for mouse ESC self-renewal and pluripotency and that this effect is mediated by DNA methylation and the Ras signaling pathway. Self-renewal Pluripotency Embryonic stem cells Chen, Bohan verfasserin aut Su, Guangsong verfasserin aut Chen, Jun verfasserin aut Guo, Dianhao verfasserin aut Yin, Qingqing verfasserin aut Wang, Wenbin verfasserin aut Zhao, Zhongfang verfasserin aut Zhang, Lei verfasserin aut Shi, Jiandang verfasserin aut Lu, Wange verfasserin aut Enthalten in Stem cell research Amsterdam [u.a.] : Elsevier, 2007 49 Online-Ressource (DE-627)548125856 (DE-600)2393143-7 (DE-576)284748463 1876-7753 nnns volume:49 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA 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_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 49
allfieldsSound	10.1016/j.scr.2020.102097 doi (DE-627)ELV010568093 (ELSEVIER)S1873-5061(20)30398-6 DE-627 ger DE-627 rda eng 570 VZ Chen, Shaohui verfasserin aut Branched-chain amino acid aminotransferase-1 regulates self-renewal and pluripotency of mouse embryonic stem cells through Ras signaling 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The developmental plasticity of embryonic stem cells (ESCs) is mainly controlled by well-characterized transcription factors, but additional factors, especially those related to metabolism that modulate this intrinsic program remain elusive. Here, using whole transcriptome analysis, we identified branched-chain amino acid aminotransferase-1(Bcat1) as highly-expressed in mouse ESCs and dramatically down-regulated upon differentiation. Bcat1 deletion impaired pluripotency and self-renewal in mouse ESCs, while Bcat1 overexpression resulted in robust ESC self-renewal and inhibition of differentiation. Whole genome bisulfite sequencing (WGBS) analysis showed that Bcat1 deletion altered whole genome methylation levels and hence gene expression in multiple pathways. Specifically, Bcat1 deletion increased expression of RAS protein activator like 1(Rasal1), leading to inactivation of Ras-Erk/MAPK signaling, while Rasal1 inhibition rescued defects seen in Bcat1 deleted cells. In summary, we demonstrate that Bcat1 is essential for mouse ESC self-renewal and pluripotency and that this effect is mediated by DNA methylation and the Ras signaling pathway. Self-renewal Pluripotency Embryonic stem cells Chen, Bohan verfasserin aut Su, Guangsong verfasserin aut Chen, Jun verfasserin aut Guo, Dianhao verfasserin aut Yin, Qingqing verfasserin aut Wang, Wenbin verfasserin aut Zhao, Zhongfang verfasserin aut Zhang, Lei verfasserin aut Shi, Jiandang verfasserin aut Lu, Wange verfasserin aut Enthalten in Stem cell research Amsterdam [u.a.] : Elsevier, 2007 49 Online-Ressource (DE-627)548125856 (DE-600)2393143-7 (DE-576)284748463 1876-7753 nnns volume:49 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA 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_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 49
language	English
source	Enthalten in Stem cell research 49 volume:49
sourceStr	Enthalten in Stem cell research 49 volume:49
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Self-renewal Pluripotency Embryonic stem cells
dewey-raw	570
isfreeaccess_bool	false
container_title	Stem cell research
authorswithroles_txt_mv	Chen, Shaohui @@aut@@ Chen, Bohan @@aut@@ Su, Guangsong @@aut@@ Chen, Jun @@aut@@ Guo, Dianhao @@aut@@ Yin, Qingqing @@aut@@ Wang, Wenbin @@aut@@ Zhao, Zhongfang @@aut@@ Zhang, Lei @@aut@@ Shi, Jiandang @@aut@@ Lu, Wange @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
hierarchy_top_id	548125856
dewey-sort	3570
id	ELV010568093
language_de	englisch
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author	Chen, Shaohui
spellingShingle	Chen, Shaohui ddc 570 misc Self-renewal misc Pluripotency misc Embryonic stem cells Branched-chain amino acid aminotransferase-1 regulates self-renewal and pluripotency of mouse embryonic stem cells through Ras signaling
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topic_title	570 VZ Branched-chain amino acid aminotransferase-1 regulates self-renewal and pluripotency of mouse embryonic stem cells through Ras signaling Self-renewal Pluripotency Embryonic stem cells
topic	ddc 570 misc Self-renewal misc Pluripotency misc Embryonic stem cells
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title	Branched-chain amino acid aminotransferase-1 regulates self-renewal and pluripotency of mouse embryonic stem cells through Ras signaling
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title_full	Branched-chain amino acid aminotransferase-1 regulates self-renewal and pluripotency of mouse embryonic stem cells through Ras signaling
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author_browse	Chen, Shaohui Chen, Bohan Su, Guangsong Chen, Jun Guo, Dianhao Yin, Qingqing Wang, Wenbin Zhao, Zhongfang Zhang, Lei Shi, Jiandang Lu, Wange
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title_sort	branched-chain amino acid aminotransferase-1 regulates self-renewal and pluripotency of mouse embryonic stem cells through ras signaling
title_auth	Branched-chain amino acid aminotransferase-1 regulates self-renewal and pluripotency of mouse embryonic stem cells through Ras signaling
abstract	The developmental plasticity of embryonic stem cells (ESCs) is mainly controlled by well-characterized transcription factors, but additional factors, especially those related to metabolism that modulate this intrinsic program remain elusive. Here, using whole transcriptome analysis, we identified branched-chain amino acid aminotransferase-1(Bcat1) as highly-expressed in mouse ESCs and dramatically down-regulated upon differentiation. Bcat1 deletion impaired pluripotency and self-renewal in mouse ESCs, while Bcat1 overexpression resulted in robust ESC self-renewal and inhibition of differentiation. Whole genome bisulfite sequencing (WGBS) analysis showed that Bcat1 deletion altered whole genome methylation levels and hence gene expression in multiple pathways. Specifically, Bcat1 deletion increased expression of RAS protein activator like 1(Rasal1), leading to inactivation of Ras-Erk/MAPK signaling, while Rasal1 inhibition rescued defects seen in Bcat1 deleted cells. In summary, we demonstrate that Bcat1 is essential for mouse ESC self-renewal and pluripotency and that this effect is mediated by DNA methylation and the Ras signaling pathway.
abstractGer	The developmental plasticity of embryonic stem cells (ESCs) is mainly controlled by well-characterized transcription factors, but additional factors, especially those related to metabolism that modulate this intrinsic program remain elusive. Here, using whole transcriptome analysis, we identified branched-chain amino acid aminotransferase-1(Bcat1) as highly-expressed in mouse ESCs and dramatically down-regulated upon differentiation. Bcat1 deletion impaired pluripotency and self-renewal in mouse ESCs, while Bcat1 overexpression resulted in robust ESC self-renewal and inhibition of differentiation. Whole genome bisulfite sequencing (WGBS) analysis showed that Bcat1 deletion altered whole genome methylation levels and hence gene expression in multiple pathways. Specifically, Bcat1 deletion increased expression of RAS protein activator like 1(Rasal1), leading to inactivation of Ras-Erk/MAPK signaling, while Rasal1 inhibition rescued defects seen in Bcat1 deleted cells. In summary, we demonstrate that Bcat1 is essential for mouse ESC self-renewal and pluripotency and that this effect is mediated by DNA methylation and the Ras signaling pathway.
abstract_unstemmed	The developmental plasticity of embryonic stem cells (ESCs) is mainly controlled by well-characterized transcription factors, but additional factors, especially those related to metabolism that modulate this intrinsic program remain elusive. Here, using whole transcriptome analysis, we identified branched-chain amino acid aminotransferase-1(Bcat1) as highly-expressed in mouse ESCs and dramatically down-regulated upon differentiation. Bcat1 deletion impaired pluripotency and self-renewal in mouse ESCs, while Bcat1 overexpression resulted in robust ESC self-renewal and inhibition of differentiation. Whole genome bisulfite sequencing (WGBS) analysis showed that Bcat1 deletion altered whole genome methylation levels and hence gene expression in multiple pathways. Specifically, Bcat1 deletion increased expression of RAS protein activator like 1(Rasal1), leading to inactivation of Ras-Erk/MAPK signaling, while Rasal1 inhibition rescued defects seen in Bcat1 deleted cells. In summary, we demonstrate that Bcat1 is essential for mouse ESC self-renewal and pluripotency and that this effect is mediated by DNA methylation and the Ras signaling pathway.
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title_short	Branched-chain amino acid aminotransferase-1 regulates self-renewal and pluripotency of mouse embryonic stem cells through Ras signaling
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author2	Chen, Bohan Su, Guangsong Chen, Jun Guo, Dianhao Yin, Qingqing Wang, Wenbin Zhao, Zhongfang Zhang, Lei Shi, Jiandang Lu, Wange
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doi_str	10.1016/j.scr.2020.102097
up_date	2024-07-06T18:26:58.815Z
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Branched-chain amino acid aminotransferase-1 regulates self-renewal and pluripotency of mouse embryonic stem cells through Ras signaling

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