Activin A in combination with ERK1/2 MAPK pathway inhibition sustains propagation of mouse embryonic stem cells
详细信息 查看全文
- 作者：Yuhei Ashida ; May Nakajima-Koyama ; Akira Hirota ; Takuya Yamamoto and Eisuke Nishida
- 刊名：Genes to Cells
- 出版年：2017
- 出版时间：February 2017
- 年：2017
- 卷：22
- 期：2
- 页码：189-202
- 全文大小：1259K
- ISSN：1365-2443
文摘
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.