报告题目: 利用单细胞测序技术解析X染色体失活在早期发育过程中与细胞全能性和分化的关系
报告人: 陈庚 副研究员
主持人: 石铁流 教授
报告时间: 12月14日 13:30-15:00 (周三下午) 结束时间:
报告地点: 闵行校区天美娱乐534报告厅
报告人简介:陈庚是今年新入职于天美娱乐的副研究员😜。其2009年9月至2014年6月在天美娱乐硕博连读,之后在复旦大学和瑞典卡罗林斯卡医天美做博后。目前已经在Genome Research📙、Nature Communications🦎、Scientific Reports、RNA等国际SCI杂志发表一作论文14篇,其中今年发表在Genome Research上的一作论文被选为封面文章。其研究方向为生物信息学,主要是基于基因组🩳🧛🏻、转录组🏇🏽、蛋白质组等多组学高通量测序数据研究相应的分子生物学功能和疾病的致病机理等。
报告摘要👵🏽:Pluripotency, differentiation, and X Chromosome inactivation (XCI) are key aspects of embryonic development. However, the underlying relationship and mechanisms among these processes remain unclear. We systematically dissected these features along developmental progression using mouse embryonic stem cells (mESCs) and single-cell RNA sequencing with allelic resolution. We found that mESCs grown in a ground state 2i condition displayed transcriptomic profiles diffused from preimplantation mouse embryonic cells, whereas EpiStem cells closely resembled the post-implantation epiblast. Sex-related gene expression varied greatly across distinct developmental states. We also identified novel markers that were highly enriched in each developmental state. Moreover, we revealed that several novel pathways, including PluriNetWork and Focal Adhesion, were responsible for the delayed progression of female EpiStem cells. Importantly, we “digitalized” XCI progression using allelic expression of active and inactive X Chromosomes and surprisingly found that XCI states exhibited profound variability in each developmental state, including the 2i condition. XCI progression was not tightly synchronized with loss of pluripotency and increase of differentiation at the single-cell level, although these processes were globally correlated. In addition, highly expressed genes, including core pluripotency factors, were in general biallelically expressed. Taken together, our study sheds light on the dynamics of XCI progression and the asynchronicity between pluripotency, differentiation, and XCI.