先驱因素ETV2通过招募抑制器REST来保护内皮细胞特异性,以限制替代血统承诺
bioRxiv : the preprint server for biology
|June 10, 2024
概括
先进的ETV2因子通过指导间皮细胞的祖先来驱动内皮细胞 (EC) 规范. ETV2招募抑制器REST来阻止替代细胞命运,从而实现高效的EC血统承诺.
科学领域:
- 发展生物学 发展生物学
- 再生医学是一种再生医学.
- 干细胞生物学 干细胞生物学
背景情况:
- 细胞命运规范对于发展和再生医学至关重要.
- ETV2是调节内皮细胞 (EC) 谱系规范的关键先驱因素.
研究的目的:
- 阐明ETV2驱动的EC命运规范的分子机制.
- 描述ETV2介导的EC差异化过程中的转录组和染色质景观.
- 确定参与ETV2在EC规范中的作用的辅助因子.
主要方法:
- 利用一个系统,引导人类诱导的多能干细胞衍生中皮细胞前代形成ECs.
- 应用CUT&RUN,单细胞RNA测序 (scRNA-seq) 和scATAC-seq用于分子分析.
- 对基本辅助因子进行功能查和候选者验证.
主要成果:
- 定义了ETV2的开拓性活动的范围,并确定了直接下游目标.
- 证明ETV2指导EC祖先的特异性,并抑制替代命运.
- 确定了GABPA作为转录激活剂和REST作为EC规范的关键抑制剂.
- 显示ETV2招募REST来抑制非EC血统基因.
结论:
- 通过调节基因表达和染色质可访问性,ETV2充当了EC规范的主调节者.
- 像ETV2这样的先驱因素可以招募抑制器 (例如REST),通过抑制替代细胞命运来强制执行血统承诺.
- 这项研究提供了对EC分化的高分辨率分子理解,这对于再生医学应用至关重要.
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