SOX1 Is Required for the Specification of Rostral Hindbrain Neural Progenitor Cells from Human Embryonic Stem Cells
SOX1 Is Required for the Specification of Rostral Hindbrain Neural Progenitor Cells from Human Embryonic Stem Cells
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SOX1 是人胚胎干细胞头侧后脑神经祖细胞规格所必需的
DOI：
10.1016/j.isci.2020.101475
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发表时间：
2020-09-25
期刊：
影响因子：
5.8
通讯作者：
Jin, Ying
中科院分区：
文献类型：
--
作者：
Liu, Xinyuan;Fang, Zhuoqing;Jin, Ying
区域特异性神经祖细胞（NPC）可以通过调节信号通路从人胚胎干细胞（hESC）产生。然而，如何内在的转录因子有助于神经区域化没有得到很好的表征。在这里，我们从hESC中产生区域特异性NPC，并发现SOX 1在具有喙状后脑身份的NPC中高度表达。此外，我们发现OTX 2抑制SOX 1的表达，显示两个因子之间的排他性表达。此外，SOX 1敲除（KO）导致中脑基因的上调和头端后脑基因的下调，表明SOX 1是头端后脑NPC特化所必需的。我们的SOX 1染色质免疫沉淀测序分析显示，SOX 1结合到GBX 2的远端区域，以激活其表达。GBX 2的过表达在很大程度上消除了SOX 1-KO诱导的异常基因表达。综上所述，本研究揭示了SOX 1在早期神经区域化中未被认识的作用，并为精确控制OTX 2/GBX 2界面提供了新的信息。
Region-specific neural progenitor cells (NPCs) can be generated from human embryonic stem cells (hESCs) by modulating signaling pathways. However, how intrinsic transcriptional factors contribute to the neural regionalization is not well characterized. Here, we generate region-specific NPCs from hESCs and find that SOX1 is highly expressed in NPCs with the rostral hindbrain identity. Moreover, we find that OTX2 inhibits SOX1 expression, displaying exclusive expression between the two factors. Furthermore, SOX1 knockout (KO) leads to the upregulation of midbrain genes and downregulation of rostral hindbrain genes, indicating that SOX1 is required for specification of rostral hindbrain NPCs. Our SOX1 chromatin immunoprecipitation sequencing analysis reveals that SOX1 binds to the distal region of GBX2 to activate its expression. Overexpression of GBX2 largely abrogates SOX1-KO-induced aberrant gene expression.Taken together, this study uncovers previously unappreciated role of SOX1 in early neural regionalization and provides new information for the precise control of the OTX2/GBX2 interface.