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人类胎儿脏有机体模型早期人类生和Notch驱动的细胞命运
Michael Namestnikov1,2,3, Osnat Cohen-Zontag1,3, Dorit Omer1
1The Pediatric Stem Cell Research Institute and Pediatric Nephrology Division, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel HaShomer, Israel.
The EMBO journal
|July 21, 2025
概括
人类胎儿器官 (hFKOs) 在体外培养以模拟发育. 这些hFKOs为多能干细胞衍生器官提供了基准,并揭示了脏发育和Notch信号的洞察力.
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
- 再生医学是一种再生医学.
背景情况:
- 多能干细胞 (PSC) 衍生的器官是研究人类发育和疾病的宝贵工具.
- 需要人类胎儿脏发育的可访问模型来对PSC衍生器官进行基准测试.
研究的目的:
- 建立长期体外培养人类胎儿脏衍生器官 (hFKOs) 的协议.
- 利用hFKOs作为研究人类脏发育和比较PSC衍生器官的模型.
- 通过使用hFKOs调查Notch信号在人类发育中的作用.
主要方法:
- 化学定义,人类胎儿脏细胞的无血清培养.
- 在体外有机体形成和长期培养.
- 大量转录组学,单细胞RNA测序,伪时间分析和免疫染.
- 药理上抑制了诺奇信号的发生.
主要成果:
- hFKOs自组织成两极分化的上皮质,重复结合和尿道芽系.
- 鉴定了多种细胞种群,具有保存的上皮原生细胞和管状分化.
- 缺口抑制导致成熟阻断,原体增加,并转向远端管道命运.
- 鉴定出一种新型的表达prominin-1的细胞状态,可以绕过Notch抑制.
结论:
- hFKOs为研究人类脏发育提供了一个忠实的体外模型.
- 该模型通过提供PSC衍生器官的基准来推进干细胞生物学和再生医学.
- 获得了对Notch信号通路和发育中的细胞状态可塑性的洞察力.
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