尿路上皮质和远端脏之间的体外可塑性和成熟度是由细胞外信号控制的
Pamela Kairath1, Pei Xuan Er1, Sean Wilson1
1Murdoch Children's Research Institute, Parkville, Melbourne, 3052, Australia.
Developmental biology
|February 18, 2026
概括
人类多能干细胞可以分化为脏组织,形成管和尿道上皮. 微环境影响细胞身份,在体外证明了这些细胞类型之间的可塑性.
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
- 脏生物学 脏生物学
背景情况:
- 人类多能干细胞 (hPSCs) 可以分化为尿路上皮质,它在胚胎发育期间来自管,形成脏收集管道.
- 以前的研究表明,hPSC衍生的远端上皮可以获得尿道表型,这种可塑性在自然胚胎发生过程中没有观察到.
研究的目的:
- 用RETtdTomato和GATA3mCherry的记者线来研究hPSC衍生的远膜表皮的可塑性.
- 探索管,尿道上皮和远端脏状态之间的体外连续性,以及微环境在细胞身份中的作用.
主要方法:
- 从hPSCs中诱导前间介质质皮.
- 添加RSPO1以诱导非稳定性脏细胞的模式.
- 差异化表皮质的ex vivo共同培养和Matrigel播种以评估表型可塑性.
主要成果:
- 在前间介质中皮层诱导后自发形成类似管的上皮质结质.
- 添加RSPO1导致了脱节的脏 (遥远的卷曲管,厚厚的上升四肢),但缺乏近端细分和球体.
- 表皮表现出可塑性,在共同培养中采用尿路表皮或管状状态,并在Matrigel中播种时采用尿路尖端身份.
结论:
- 这项研究强调了管,尿道上皮和来自hPSCs的远端膜表型之间的体外连续性.
- 这些发现强调了微环境在发育模型中决定细胞身份和可塑性的重要作用.
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