Activin A in combination with ERK1/2 MAPK pathway inhibition sustains propagation of mouse embryonic stem cells
Activin A in combination with ERK1/2 MAPK pathway inhibition sustains propagation of mouse embryonic stem cells
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DOI：
10.1111/gtc.12467
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发表时间：
2017-02-01
期刊：
影响因子：
2.1
通讯作者：
Nishida, Eisuke
中科院分区：
文献类型：
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作者：
Ashida, Yuhei;Nakajima-Koyama, May;Nishida, Eisuke
激活素/Nodal/TGF-β信号通路在维持小鼠上胚层干细胞（EpiSC）中起主要作用。含有激活素A和bFGF的EpiSC维持培养基诱导小鼠胚胎干细胞（ESC）分化为EpiSC。在这里，我们表明，激活素A也有能力有效地繁殖胚胎干细胞，而不分化为EpiSC时，与MEK抑制剂PD 0325901组合。在激活素+PD中培养的ESC保持幼稚多能性相关转录因子的高水平表达。全基因组分析显示，在激活素+PD中培养的ESC的基因表达谱类似于在2 i.在激活素+PD中培养的ESC还显示出与ESC的幼稚多能性共同的特征，包括优先使用Oct 4远端增强子和对Wnt途径激活的自我更新应答。我们的发现显示了激活素/Nodal/TGF-β信号在稳定ESCs自我更新基因调控网络中的作用。
The Activin/Nodal/TGF-beta 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-beta signaling in stabilizing self-renewal gene regulatory networks in ESCs.