管理胚外内皮细胞命运选择的转录网络
Paula Duyen Pham1, Hanbin Lu2, Han Han1
1Department of Developmental and Cell Biology, University of California, Irvine, CA, 92697, USA.
Developmental biology
|July 9, 2023
概括
转录因子GATA6,SOX17和FOXA2调节原始内皮 (PrE) 细胞命运决定. 这些因素通过调节参与细胞身份和自我更新的关键基因来控制表皮内皮 (PE) 和内皮内皮 (VE) 血统分歧.
科学领域:
- 发展生物学 发展生物学
- 干细胞生物学 干细胞生物学
- 基因规则 基因规则
背景情况:
- 原始内皮体 (PrE) 祖先的分化途径变成顶膜内皮体 (PE) 和内皮内皮体 (VE) 细胞命运尚未完全理解.
- 转录因子 (TF) 网络在指导细胞类型特定的基因表达程序方面发挥着至关重要的作用.
研究的目的:
- 阐明分子机制和核心基因调控模块,控制PE-VE系从PrE祖先的分支.
- 为了确定关键的转录因子和它们的相互作用,在内皮系内决定细胞命运选择.
主要方法:
- 单细胞转录组分析以定义PrE,PE和VE细胞状态.
- 针对PE和VE细胞特有的活性增强剂的表观基因组比较.
- 功能性研究涉及在体外PE细胞模型 (cXEN细胞) 中急性耗尽GATA6,SOX17和FOXA2,包括RNA测序.
主要成果:
- GATA6,SOX17和FOXA2被确定为PE-VE血统分歧的中央调节者.
- 通过诱导MYCN和抑制VE基因,GATA6和SOX17促进PE命运,而FOXA2抑制MYCN并激活VE基因.
- 这些TF的对抗性监管活动和增强器联合结合解释了PrE谱系的可塑性.
- 证明BMP信号通过激活VE TFs和抑制像GATA6和SOX17这样的PE TFs来促进VE命运.
结论:
- 一个涉及GATA6,SOX17和FOXA2的核心基因调节模块控制PE和VE细胞命运的决定.
- 这些转录因子在调节细胞身份和可塑性方面表现出相反的作用.
- 像BMP信号这样的外部线索与这个TF网络集成,从而影响细胞命运的决定.
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