血液造血干细胞发育中的信号要求从血源性内皮细胞转变为血源性内皮细胞
Saori Morino-Koga1, Mariko Tsuruda1, Xueyu Zhao1
1Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.
概括
干细胞因子 (SCF) 和血栓形成素 (TPO) 诱导来自胚胎细胞的造血干细胞 (HSC). 早期胚胎细胞需要内皮细胞支持HSC诱导,突出显示在发育过程中信号需求的变化.
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
- 干细胞生物学 干细胞生物学
背景情况:
- 造血干细胞 (HSC) 起源于小鼠胚胎生成过程中的血源性内皮细胞 (HEC).
- 在体外,前HSC-I和前HSC-II细胞可以分化为HSC,但所需的诱导因子尚不清楚.
研究的目的:
- 为了确定在体外从HEC诱导HSC的最小因子.
- 从HEC来研究HSC开发过程中信号要求的变化.
主要方法:
- 使用干细胞因子 (SCF) 和血栓形成素 (TPO) 的无血清和无料培养条件.
- 在胚胎日 (E) 10.5至11.5使用单细胞RNA测序,背上大动脉和胎儿肝脏.
- 分析了E10.5 HECs,E10.5 pre-HSC-I和E11.5 pre-HSC-I的差异化潜力.
主要成果:
- 在没有额外的支持的情况下,SCF和TPO诱导从E11.5到HSC-I之前的插入HSC.
- 在HSC-I和HEC之前的E10.5需要一个内皮细胞层与SCF和TPO一起进行HSC分化.
- 在肝细胞中检测到TPO,而SCF表达更广泛,包括内皮细胞和肝细胞.
结论:
- 从HEC到HSC的发展显示了信号要求的转变.
- 早期分化 (E10.5 HECs到E11.5 pre-HSC-I) 取决于SCF和内皮因子.
- 晚期的分化 (从E11.5前HSC-I到HSC) 是由SCF和TPO驱动的,特别是在胎儿肝脏中.
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