Activin A in combination with ERK1/2 MAPK pathway inhibition sustains propagation of mouse embryonic stem cells

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. Activin A has an ability to efficiently propagate ESCs when combined with a MEK inhibitor PD0325901. ESCs cultured in Activin+PD show naive pluripotency features, including the gene expression profile, the preferential usage of the Oct4 distal enhancer, and the self‐renewal response to Wnt signaling pathway activation.
Source: Genes to Cells - Category: Genetics & Stem Cells Authors: Tags: Original Article Source Type: research