Activin/Nodal signaling and NANOG orchestrate human embryonic stem cell fate decisions

Human embryonic stem cells are capable to self-renew while maintaining the capacity to differentiate into a broad diversity of cell types. Activin/Nodal signalling pathway is essential to maintain the pluripotent state of hESCs but also to drive their differentiation toward the endoderm germ layer. This manuscript describes the mechanisms by which Activin/Nodal signalling interact with histone modifiers complexes to control H34me3 in hESCs. In vivo analyses also confirmed that these mechanisms could be applied to the gastrulating mouse embryos. These results illustrate how extra-cellular pathways can regulate the epigenetic state of pluripotent stem cells in vitro and during embryonic development.

Full article in Genes & Development

Publication details:

Bertero A, Madrigal P, Galli A, Hubner NC, Moreno I, Burks D, Brown S, Pedersen RA, Gaffney D, Mendjan S, Pauklin S, Vallier L. Activin/Nodal signaling and NANOG orchestrate human embryonic stem cell fate decisions by controlling the H3K4me3 chromatin mark. Genes & Development. PMID: 25805847

 

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Activin/Nodal controls H3K4me3 in human embryonic stem cells (hESCs) and in the mouse epiblast. Activin/Nodal maintains H3K4me3 on pluripotency and mesendoderm genes by driving SMAD2/3 and NANOG-dependent recruitment of COMPASS histone methyltransferases. Pharmacological or genetic disruption of this mechanism results into loss of pluripotency and neuroectoderm differentiation.

Image credit: Alessandro Bertero

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