Single-cell chromatin accessibility profiling of cell-state-specific gene regulatory programs during mouse organogenesis

小鼠器官发生过程中细胞状态特异性基因调控程序的单细胞染色质可及性分析

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作者:Qiuting Deng, Shengpeng Wang, Zijie Huang, Qing Lan, Guangyao Lai, Jiangshan Xu, Yue Yuan, Chang Liu, Xiumei Lin, Weimin Feng, Wen Ma, Mengnan Cheng, Shijie Hao, Shanshan Duan, Huiwen Zheng, Xiaoyan Chen, Yong Hou, Yingjie Luo, Longqi Liu, Chuanyu Liu

Abstract

In mammals, early organogenesis begins soon after gastrulation, accompanied by specification of various type of progenitor/precusor cells. In order to reveal dynamic chromatin landscape of precursor cells and decipher the underlying molecular mechanism driving early mouse organogenesis, we performed single-cell ATAC-seq of E8.5-E10.5 mouse embryos. We profiled a total of 101,599 single cells and identified 41 specific cell types at these stages. Besides, by performing integrated analysis of scATAC-seq and public scRNA-seq data, we identified the critical cis-regulatory elements and key transcription factors which drving development of spinal cord and somitogenesis. Furthermore, we intersected accessible peaks with human diseases/traits-related loci and found potential clinical associated single nucleotide variants (SNPs). Overall, our work provides a fundamental source for understanding cell fate determination and revealing the underlying mechanism during postimplantation embryonic development, and expand our knowledge of pathology for human developmental malformations.

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