BMP通过Bcl11b调节的NuRD复合体抑制Wnt信号传递,以维持肠道干细胞
Yehua Li1, Xiaodan Wang1, Meimei Huang1
1The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
The EMBO journal
|October 21, 2024
概括
Bcl11b通过增强Wnt信号传递来维持肠道干细胞,这对于肠道再生至关重要. BMP信号抑制了Bcl11b,揭示了平衡肠道平衡和修复的关键机制.
科学领域:
- 胃肠道学和肝病学
- 分子生物学分子生物学
- 干细胞生物学 干细胞生物学
背景情况:
- Lgr5+肠干细胞 (ISC) 对于肠表皮的更新和修复至关重要.
- 在ISC调节中,Wnt和BMP信号通路之间的相互作用尚未完全阐明.
研究的目的:
- 研究Bcl11b在维持Lgr5+ISC和肠道再生中的作用.
- 阐明BMP信号通过Bcl11b影响Wnt信号的机制.
主要方法:
- 在Bcl11b缺乏的小鼠和有机体中分析Lgr5+ISC种群.
- 研究Bcl11b在调节Wnt目标基因中的分子功能.
- 在没有Bcl11b的情况下,对照射和DSS诱导的炎症后肠道修复的评估.
主要成果:
- BMP信号降低了Bcl11b的调节,从而增强了Wnt信号,以维持Lgr5+的ISC.
- Bcl11b功能的丧失显著降低了Lgr5+ISC,并损害了肠道再生.
- Bcl11b抑制了NuRD复合体,并促进了β-catenin-TCF4相互作用,促进了Wnt目标基因表达.
- Bcl11b促进肠道修复,抑制结直肠癌细胞的增殖和瘤发生.
结论:
- BMP信号通过Bcl11b抑制Wnt信号,从而调节肠道恒温和再生.
- Bcl11b是肠干细胞功能和上皮细胞修复的关键调节者.
- 针对Bcl11b介导途径可能为肠道疾病和结直肠癌提供治疗策略.
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