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

AI Article Synopsis

  • Developmental biologists have observed that embryonic cells have varying potentials to become different cell types, with recent findings highlighting two distinct states of pluripotency in embryonic stem cells (ESCs): naive and primed.
  • The study reveals that the enzyme nicotinamide N-methyltransferase (NNMT) plays a crucial role in regulating pluripotency in human embryonic stem cells (hESCs) by influencing their metabolic state.
  • In naive hESCs, high levels of NNMT lead to decreased S-adenosyl methionine (SAM), which affects gene repression and activation pathways, suggesting that metabolism impacts the epigenetic regulation during early human development.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4662931PMC
http://dx.doi.org/10.1038/ncb3264DOI Listing

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