Liu Xinyuan, Fang Zhuoqing, Wen Jing, Tang Fan, Liao Bing, Jing Naihe, Lai Dongmei, Jin Ying
CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, CAS Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Department of Histoembryology, Genetics and Developmental Biology, Shanghai Key Laboratory of Reproductive Medicine, Shanghai JiaoTong University School of Medicine, 225 South Chongqing Road, Shanghai 200025, China.
iScience. 2020 Aug 20;23(9):101475. doi: 10.1016/j.isci.2020.101475. eCollection 2020 Sep 25.
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, 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 to activate its expression. Overexpression of largely abrogates -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.
通过调节信号通路，可以从人类胚胎干细胞（hESCs）中生成区域特异性神经祖细胞（NPCs）。然而，内在转录因子如何促进神经区域化尚未得到充分表征。在这里，我们从hESCs中生成了区域特异性NPCs，并发现SOX1在具有后脑前端特征的NPCs中高度表达。此外，我们发现OTX2抑制SOX1表达，这两种因子之间呈现排他性表达。此外，基因敲除（KO）导致中脑基因上调和后脑前端基因下调，表明SOX1是后脑前端NPCs特化所必需的。我们的SOX1染色质免疫沉淀测序分析表明，SOX1与[具体基因名称]的远端区域结合以激活其表达。[具体基因名称]的过表达在很大程度上消除了基因敲除诱导的异常基因表达。综上所述，本研究揭示了SOX1在早期神经区域化中以前未被认识的作用，并为精确控制OTX2/GBX2界面提供了新信息。
