小肠中的储备干细胞群使得Lgr5阳性细胞变得不可或缺
Hua Tian1, Brian Biehs, Søren Warming
1Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
Nature
|September 20, 2011
概括
在肠道中,表达Bmi1的干细胞可以取代表达Lgr5的细胞,保持组织再生. 这揭示了干细胞层次结构,其中Bmi1细胞补偿Lgr5细胞损失.
科学领域:
- 胃肠病学 胃肠病学
- 干细胞生物学 干细胞生物学
- 发展生物学 发展生物学
背景情况:
- 小肠上皮是高度再生的,有两个已识别的干细胞种群:Lgr5表达 (密码基础) 和Bmi1表达 (密码基础以上).
- 这两个上皮干细胞池之间的不同作用和相互关系仍然不清楚.
研究的目的:
- 研究小肠中Lgr5表达和Bmi1表达干细胞之间的功能关系.
- 要确定Lgr5表达细胞是否对肠道平衡至关重要.
主要方法:
- 在小鼠中基因可诱导命运映射.
- 使用喉毒素受体 (DTR) 系统对Lgr5表达细胞进行特异性切除.
- 血统追踪可以追踪细胞起源和后代.
主要成果:
- 完全切除Lgr5表达细胞并没有破坏肠道平衡,这表明有补偿机制.
- 在Lgr5细胞损失后,表达Bmi1的细胞增加了后代的产生,弥补了它们的消除.
- 谱系追踪证实,表达Bmi1的细胞可以产生表达Lgr5的细胞,从而建立了干细胞等级.
结论:
- 对于正常的肠道平衡来说,Lgr5表达细胞是不可缺少的.
- Bmi1表达细胞可以作为替代干细胞池,补偿Lgr5细胞损失.
- 在受伤期间,表达Bmi1的干细胞可以作为储备池,并在正常情况下补充Lgr5细胞.
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