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Comprehensive profiling reveals mechanisms of SOX2-mediated cell fate specification in human ESCs and NPCs
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Comprehensive profiling reveals mechanisms of SOX2-mediated cell fate specification in human ESCs and NPCs
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Journal Article
Comprehensive profiling reveals mechanisms of SOX2-mediated cell fate specification in human ESCs and NPCs
2016
Overview
SOX2 is a key regulator of multiple types of stem cells, especially embryonic stem cells （ESCs） and neural progen- itor cells （NPCs）. Understanding the mechanism underlying the function of SOX2 is of great importance for realizing the full potential of ESCs and NPCs. Here, through genome-wide comparative studies, we show that SOX2 executes its distinct functions in human ESCs （hESCs） and hESC-derived NPCs （hNPCs） through cell type- and stage-depen- dent transcription programs. Importantly, SOX2 suppresses non-neural lineages in hESCs and regulates neurogene- sis from hNPCs by inhibiting canonical Wnt signaling. In hESCs, SOX2 achieves such inhibition by direct transcrip- tional regulation of important Wnt signaling modulators, WLS and SFRP2. Moreover, SOX2 ensures pluripotent epigenetic landscapes via interacting with histone variant H2A.Z and recruiting polycomb repressor complex 2 to poise developmental genes in hESCs. Together, our results advance our understanding of the mechanism by which cell type-specific transcription factors control lineage-specific gene expression programs and specify cell fate.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Biomedical and Life Sciences
/ Embryonic Stem Cells - metabolism
/ Gene Expression Regulation, Developmental - genetics
/ Humans
/ Neural Stem Cells - metabolism
/ NPC
/ Original
/ Pluripotent Stem Cells - metabolism
/ SOXB1 Transcription Factors - metabolism
/ Transcription Factors - metabolism
/ Transcription, Genetic - genetics
/ 人类胚胎干细胞
/ 介导
/ 机制
/ 神经前体细胞
/ 细胞类型
/ 转录因子
/ 阶段性影响
