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The metabolome regulates the epigenetic landscape during naive-to-primed human embryonic stem cell transition.

Authors :
Sperber, Henrik
Sperber, Henrik
Mathieu, Julie
Wang, Yuliang
Ferreccio, Amy
Hesson, Jennifer
Xu, Zhuojin
Fischer, Karin A
Devi, Arikketh
Detraux, Damien
Gu, Haiwei
Battle, Stephanie L
Showalter, Megan
Valensisi, Cristina
Bielas, Jason H
Ericson, Nolan G
Margaretha, Lilyana
Robitaille, Aaron M
Margineantu, Daciana
Fiehn, Oliver
Hockenbery, David
Blau, C Anthony
Raftery, Daniel
Margolin, Adam A
Hawkins, R David
Moon, Randall T
Ware, Carol B
Ruohola-Baker, Hannele
Sperber, Henrik
Sperber, Henrik
Mathieu, Julie
Wang, Yuliang
Ferreccio, Amy
Hesson, Jennifer
Xu, Zhuojin
Fischer, Karin A
Devi, Arikketh
Detraux, Damien
Gu, Haiwei
Battle, Stephanie L
Showalter, Megan
Valensisi, Cristina
Bielas, Jason H
Ericson, Nolan G
Margaretha, Lilyana
Robitaille, Aaron M
Margineantu, Daciana
Fiehn, Oliver
Hockenbery, David
Blau, C Anthony
Raftery, Daniel
Margolin, Adam A
Hawkins, R David
Moon, Randall T
Ware, Carol B
Ruohola-Baker, Hannele
Source :
Nature cell biology; vol 17, iss 12, 1523-1535; 1465-7392
Publication Year :
2015

Abstract

For nearly a century developmental biologists have recognized that cells from embryos can differ in their potential to differentiate into distinct cell types. Recently, it has been recognized that embryonic stem cells derived from both mice and humans exhibit two stable yet epigenetically distinct states of pluripotency: naive and primed. We now show that nicotinamide N-methyltransferase (NNMT) and the metabolic state regulate pluripotency in human embryonic stem cells (hESCs). Specifically, in naive hESCs, NNMT and its enzymatic product 1-methylnicotinamide are highly upregulated, and NNMT is required for low S-adenosyl methionine (SAM) levels and the H3K27me3 repressive state. NNMT consumes SAM in naive cells, making it unavailable for histone methylation that represses Wnt and activates the HIF pathway in primed hESCs. These data support the hypothesis that the metabolome regulates the epigenetic landscape of the earliest steps in human development.

Details

Database :
OAIster
Journal :
Nature cell biology; vol 17, iss 12, 1523-1535; 1465-7392
Notes :
application/pdf, Nature cell biology vol 17, iss 12, 1523-1535 1465-7392
Publication Type :
Electronic Resource
Accession number :
edsoai.on1287394108
Document Type :
Electronic Resource