一个NOTCH4内子28调节元件控制动脉特异性和hPSCs的淋巴发育
Ho Sun Jung1, Divine Mensah Sedzro1, Peng Liu2
1Wisconsin National Primate Research Center, University of Wisconsin Graduate School, Madison, WI.
Blood vessels, thrombosis & hemostasis
|August 6, 2025
概括
NOTCH4信号传递对于从干细胞中发展动脉和淋巴细胞至关重要. 一个特定的调节元件NOTCH4in28控制NOTCH4的表达,影响动脉和淋巴细胞前体的形成.
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
- 血液形成是血液形成的过程.
背景情况:
- NOTCH信号传递对于动脉特异化和从血源性内皮形成血造干细胞至关重要.
- 了解NOTCH信号在动脉和淋巴细胞特征中的作用对于再生医学至关重要.
研究的目的:
- 调查NOTCH信号机制对于动脉和淋巴细胞规范至关重要.
- 分析血液形成分化过程中NOTCH信号的动态变化.
主要方法:
- 在血液形成分化过程中对人类多能干细胞 (hPSCs) 的单细胞多组学分析.
- 研究了一种特定的cis调节元件 (NOTCH4in28) 和SOX17结合在NOTCH4表达中的作用.
- 使用常规和有条件的iSOX17 hPSCs进行基因操纵.
主要成果:
- 在血源性内皮细胞特异化和内皮细胞转化为血液形成过程中观察到NOTCH信号和动脉程序激活.
- 动脉内皮中的NOTCH4表达是由NOTCH4in28通过SOX17结合的cis调节元件调节的.
- 删除NOTCH4in28损害了动脉HE和淋巴细胞前体 (T和NK细胞) 的形成.
结论:
- NOTCH4及其 cis-regulatory 元素 NOTCH4in28 对于动脉规范至关重要.
- NOTCH4/NOTCH4in28通路对于hPSCs的淋巴细胞发育很重要.
- 这项研究提供了对控制早期血液形成和血管发育的分子机制的见解.
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