轴性脏命运切换显示了可根据需求调节的塑料系统
MaryAnne A Achieng1, Jack Schnell1, Connor C Fausto1
1Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at University of Southern California, Los Angeles, CA, USA.
Nature communications
|August 25, 2025
概括
人类脏发育依赖于集成的WNT,BMP和FGF信号通路. 了解器官中的这些机制揭示了性和产生细胞的潜力.
科学领域:
- 肝脏病学
- 发育生物学
- 干细胞生物学
背景情况:
- 在怀孕期间,人体脏对平衡至关重要,每颗脏发育约100万个单位.
- 确切的机制控制人类脏的轴向模式仍然不太清楚.
研究的目的:
- 研究人类脏发育中的轴向模式机制.
- 使用诱导多能干细胞 (iPSC) 衍生的器官来研究生.
- 将器官发育与体内人类发育进行比较.
主要方法:
- 使用IPSC衍生的器官产生同步.
- 使用单细胞和空间转录组分析.
- 操纵WNT,BMP和FGF信号通道.
主要成果:
- 人类脏模式是由WNT/BMP/FGF综合信号编排的.
- 一个WNT激活/BMP抑制的状态促进远端脏的身份,通过FGF成熟成厚的升级循环的亨尔细胞.
- 抑制FGF会诱导近位细胞状态,依赖于BMP信号,突出显示发育性可塑性.
结论:
- 集成的WNT,BMP和FGF信号控制人轴模式.
- 脏器官系统提供了关于脏发育可塑性的见解.
- 这项研究为按需生成细胞提供了基础.
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