Graded Nodal/Activin Signaling Governs ES Cell Fate Decisions via Differential Recruitment of Phospho-Smad2 to Oct4 and Distinct Target Gene Subsets.
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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资源简介：
The Nodal/Activin morphogens are secreted signaling molecules that form concentration gradients during early embryogenesis providing stem cells with positional information and differentiation instructions important for embryonic patterning. The molecular basis driving stem cell interpretation of signaling gradients and the undertaking of distinct cell fate decisions remains poorly understood. We show that perturbation of endogenous Nodal/Activin signaling in ES cells leads to exit from self renewal towards mesendodermal differentiation at high signaling and trophectoderm induction during low signaling. ChIP-seq of Phospho-Smad2, the downstream transcription factor of the Nodal/Activin pathway reveals binding to distinct subsets of target genes in a dose dependent manner including the promoter region of the Oct4 master regulator of stemness. Consequently, both Oct4 mRNA and protein levels are directly driven by graded Nodal/Activin signaling. Hence stem cells interpret and carry out differential Nodal/Activin signaling instructions via a corresponding gradient of Smad2 phosphorylation that selectively titers self renewal against alternative differentiation programs.
提供机构：
Genome Institute of Singapore
创建时间：
2022-02-20
