泛-ErbB负调节器Lrig1是一种肠道干细胞标记物,其功能是瘤抑制剂
Anne E Powell1, Yang Wang, Yina Li
1Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Cell
|April 3, 2012
概括
Lrig1标志着静止的肠干细胞补充受损组织. 失去Lrig1会破坏ErbB信号传递,导致肠腺瘤,突出显示它在预防新生病方面的作用.
科学领域:
- 细胞生物学 细胞生物学
- 胃肠病学 胃肠病学
- 癌症研究 癌症研究
背景情况:
- 肠道干细胞 (ISC) 对于组织平衡至关重要.
- 繁殖 (Lgr5+) 和静止的ISC种群存在.
- 调节ISC静止的分子机制尚未完全理解.
研究的目的:
- 为了识别静止肠道干细胞的分子标记.
- 阐明Lrig1在肠干细胞调节中的作用.
- 调查Lrig1,ErbB信号传递和肠道瘤之间的联系.
主要方法:
- 在小鼠模型中进行血统追踪和细胞追踪.
- 结肠干细胞Lrig1+和Lgr5+的转录组概况.
- 基因操纵 (Apc损失,Lrig1切除) 和瘤形成的分析.
主要成果:
- Lrig1确定了一个静止的,长寿的ISC在密室基地的群体.
- Lrig1+ ISCs表现出与细胞周期抑制和氧化应激反应相关的独特基因表达特征.
- 失去Lrig1会导致ErbB信号的增加,并促进十二指腺瘤的形成.
- 在Lrig1+细胞中失去Apc会诱导肠道腺瘤.
结论:
- Lrig1是肠道干细胞静止的关键调节者.
- 校准的ErbB信号,受到Lrig1等负调节者的影响,保持ISC静止.
- 干扰Lrig1介导的调节会导致肠癌的发展.
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