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
bioRxiv : the preprint server for biology
|June 12, 2025
概括
人类多能干细胞 (hPSCs) 可以产生脏尿管表皮和管状细胞. 微环境影响它们的细胞身份,在体外表现出可塑性.
科学领域:
- 发育生物学是发展生物学.
- 干细胞生物学 干细胞生物学
- 腎臟病學 (nephrology) 是一種醫學專業.
背景情况:
- 人类多能干细胞 (hPSCs) 可以分化成各种细胞类型,包括上皮.
- 尿路上皮质,起源于管,在胚胎发生过程中形成脏收集管道.
- 从hPSC衍生的远端膜上皮质可以表现出尿管表型,这种可塑性在胚胎发育中没有观察到.
研究的目的:
- 为了研究hPSC衍生的管和远端上皮质的可塑性.
- 在体外探索微环境在指导细胞身份中的作用.
- 使用记者线 (RETtdTomato和GATA3mCherry) 来跟踪细胞命运.
主要方法:
- 从hPSCs中诱导前间介质质皮.
- 将RSPO1添加到样式不稳定性脏中.
- 活体共培和Matrigel播种,以评估细胞对微环境线索的反应.
- 使用了RETtdTomato和GATA3mCherry的记者线路.
主要成果:
- 从诱导的前间介质半皮形成一个类似管的上皮质.
- 添加RSPO1导致了脱节的脏结构 (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,在共同培养条件下采用尿管或管状状态.
- 在Matrigel中播种单细胞,结果是具有RET+尿道尖端标识的球体.
结论:
- 在体外系统建立了管,尿道上皮和远端脏状态之间的连续性.
- 这种可塑性凸显了微环境对hPSC衍生的上皮质细胞身份的显著影响.
- 这些发现为脏发育和再生医学的潜在策略提供了洞察力.
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