在恒温和受伤期间,Lgr5+干细胞在肠表皮质的细胞层次中保持顶部位置
Julian Chua1,2, Lucy Driver3,4, Masahiro Narimatsu5
1Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
bioRxiv : the preprint server for biology
|November 26, 2025
概括
Lgr5+干细胞对于肠道的自我更新和修复至关重要. 在受伤后,WNT信号传递对它们的功能和再生至关重要,解决了关于肠道干细胞种群的争论.
科学领域:
- 胃肠病学 胃肠病学
- 干细胞生物学 干细胞生物学
- 分子生物学分子生物学
背景情况:
- 负责肠上皮质平衡和再生的初级干细胞种群一直在争论中.
- 最近的模型已经挑战了依赖于WNT的Lgr5+密码基柱状 (CBC) 细胞的既定作用.
研究的目的:
- 量化整合多原子数据以解决关于肠道干细胞功能的争论.
- 阐明Lgr5+ CBC细胞在肠上皮质自我更新和再生中的作用.
主要方法:
- 单细胞转录组学 单细胞转录组学
- 染色体可访问性测定
- 空间转录组学 空间转录组学
- 血统追踪分析遍及小肠的细肠.
主要成果:
- 在恒常状态下,Lgr5+细胞仅维持上皮的自我更新,需要R-spondin.
- 在受伤后,幸存的Lgr5+细胞被重新编程成类似胎儿的状态,以启动修复.
- 再生取决于WNT/β-catenin的重新激活,由TCF动机可访问性和WNT目标基因上调证明.
结论:
- Lgr5+ CBC 细胞是肠道上皮细胞自我更新和再生的中心干细胞群.
- 对于Lgr5+细胞功能和密码再生,WNT信号是不可或缺的.
- 这些发现使以前关于肠道干细胞等级的争议得以和解.
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