从胎儿肺部的新生血液形成
Anthony K Yeung1,2, Carlos Villacorta-Martin1, Jonathan Lindstrom-Vautrin1
1Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA.
Blood advances
|September 20, 2023
概括
胎儿肺部含有专门的血源性内皮细胞 (HECs),能够进行内皮细胞到血造细胞的过渡 (EHT). 这些细胞在主要发育部位之外产生新的造血干细胞和原生细胞 (HSPC).
科学领域:
- 发展生物学 发展生物学
- 血液形成 血液形成 血液形成
- 细胞生物学 细胞生物学
背景情况:
- 血源性内皮细胞 (HECs) 对于通过内皮细胞转化为内皮细胞转化 (EHT) 来产生血液形成的祖先至关重要.
- 虽然主要与大动脉 - 淋巴体 - 半神经 (AGM) 区域有关,但在其他胚胎部位也观察到了EHT.
- 肺在造血过程中的作用,包括含有造血干细胞和原生细胞 (HSPCs) 的肺部作用,表明有可能存在肺部居住的HECs.
研究的目的:
- 调查胎儿肺中的HECs的存在和功能.
- 为了确定胎儿肺部的HEC是否可以接受ETH以产生新的HSPC.
- 为了确定参与肺HEC介导的EHT的信号通路.
主要方法:
- 鼠类和人类胎儿肺部的扩展培养.
- 流细胞计测试用于评估细胞表面标记物 (EPCR,CD41,CD43,CD44).
- 单细胞RNA测序 (scRNA-seq) 和小分子调制.
主要成果:
- 胎儿肺部扩张的附着内皮细胞转化为漂浮的造血细胞,失去内皮标记物.
- 功能评估证实了表达关键EHT和HSPC前标记物的多效HSPCs的产生.
- scRNA-seq和分子研究表明,TGFβ/BMP,Notch和YAP信号通路对肺HEC EHT至关重要.
结论:
- 胎儿的肺部含有功能性的HEC,能够进行EHT.
- 这一发现确立了胎儿肺部作为新生血液形成后AGM发育的潜在外骨膜部位.
- 这些结果扩大了我们对造血干细胞起源和外母细胞造血的理解.
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