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  • Title: Activin A in combination with ERK1/2 MAPK pathway inhibition sustains propagation of mouse embryonic stem cells.
    Author: Ashida Y, Nakajima-Koyama M, Hirota A, Yamamoto T, Nishida E.
    Journal: Genes Cells; 2017 Feb; 22(2):189-202. PubMed ID: 28097777.
    Abstract:
    The Activin/Nodal/TGF-β signaling pathway plays a major role in maintaining mouse epiblast stem cells (EpiSCs). The EpiSC-maintaining medium, which contains Activin A and bFGF, induces differentiation of mouse embryonic stem cells (ESCs) to EpiSCs. Here, we show that Activin A also has an ability to efficiently propagate ESCs without differentiation to EpiSCs when combined with a MEK inhibitor PD0325901. ESCs cultured in Activin+PD retained high-level expression of naive pluripotency-related transcription factors. Genomewide analysis showed that the gene expression profile of ESCs cultured in Activin+PD resembles that of ESCs cultured in 2i. ESCs cultured in Activin+PD also showed features common to the naive pluripotency of ESCs, including the preferential usage of the Oct4 distal enhancer and the self-renewal response to Wnt pathway activation. Our finding shows a role of Activin/Nodal/TGF-β signaling in stabilizing self-renewal gene regulatory networks in ESCs.
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