Inhibition of Wnt/beta-catenin signaling by IWR1 induces expression of Foxd3 to promote mouse epiblast stem cell self-renewal
Inhibition of Wnt/beta-catenin signaling by IWR1 induces expression of Foxd3 to promote mouse epiblast stem cell self-renewal
复制标题
IWR1抑制Wnt/β-catenin信号诱导Foxd3表达促进小鼠外胚层干细胞自我更新
DOI：
10.1016/j.bbrc.2017.06.086
复制
发表时间：
2017
影响因子：
3.1
通讯作者：
Ye Shoudong
中科院分区：
文献类型：
--
作者：
Liu Kuisheng;Sun Yuanyuan;Liu Dahai;Ye Shoudong
Inhibition of Wnt/β-catenin signaling facilitates the derivation of mouse epiblast stem cells (EpiSCs), as well as dramatically promotes EpiSC self-renewal. The specific mechanism, however, is still unclear. Here, we showed that IWR1, a Wnt/β-catenin signaling inhibitor, allowed long-term self-renewal of EpiSCs in serum medium in combination with ROCK inhibitor Y27632. Through transcriptome data analysis, we arrived at a set of candidate transcription factors induced by IWR1. Among these, Forkhead box D3 (Foxd3) was most abundant. Forced expression ofFoxd3could recapitulate the self-renewal-promoting effect of IWR1 in EpiSCs. Conversely, knockdown ofFoxd3profoundly compromised responsiveness to IWR1, causing extinction of pluripotency markers and emergence of differentiation phenotype. Foxd3 thus is necessary and sufficient to mediate self-renewal downstream of Wnt/β-catenin signaling inhibitor. These findings highlight an important role for Foxd3 in regulating EpiSCs and will expand current understanding of the primed pluripotency.
