Comprehensive profiling reveals mechanisms of SOX2-mediated cell fate specification in human ESCs and NPCs
Comprehensive profiling reveals mechanisms of SOX2-mediated cell fate specification in human ESCs and NPCs
复制标题
全面的分析揭示了人类 ESC 和 NPC 中 SOX2 介导的细胞命运规范的机制
DOI：
10.1038/cr.2016.15
复制
发表时间：
2016-02-01
期刊：
影响因子：
44.1
通讯作者：
Jin, Ying
中科院分区：
文献类型：
--
作者：
Zhou, Chenlin;Yang, Xiaoqin;Jin, Ying
SOX2是多种干细胞的关键调节因子，尤其是胚胎干细胞(ESCs)和神经前体细胞(NPC)。了解SOX2的作用机制对于充分发挥ESCs和NPC的潜能具有重要意义。在这里，我们通过全基因组的比较研究表明，SOX2通过细胞类型和阶段依赖的转录程序在人胚胎干细胞(HESCs)和hESC来源的NPC(HNPC)中执行其不同的功能。重要的是，SOX2抑制hESCs中的非神经谱系，并通过抑制典型的Wnt信号来调节hNPC的神经发生。在hESCs中，SOX2通过对重要的Wnt信号调节因子WLS和SFRP2的直接转录调节来实现这种抑制。此外，SOX2通过与组蛋白变异体H2A相互作用，确保了多潜能的表观遗传景观。Z和招募多梳抑制物复合体2来平衡hESCs中的发育基因。总之，我们的结果促进了我们对细胞类型特定的转录因子控制谱系特定的基因表达程序和指定细胞命运的机制的理解。
SOX2 is a key regulator of multiple types of stem cells, especially embryonic stem cells (ESCs) and neural progenitor 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-dependent transcription programs. Importantly, SOX2 suppresses non-neural lineages in hESCs and regulates neurogenesis from hNPCs by inhibiting canonical Wnt signaling. In hESCs, SOX2 achieves such inhibition by direct transcriptional 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.