血统追踪揭示了小鼠肠腺瘤中的Lgr5+干细胞活性
Arnout G Schepers1, Hugo J Snippert, Daniel E Stange
1Hubrecht Institute, Koninklijke Nederlandse Akademie van Wetenschappen, and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, Netherlands.
Science (New York, N.Y.)
|August 3, 2012
概括
癌症干细胞促进肠腺瘤的生长. 研究人员发现,腺瘤内的Lgr5阳性细胞充当干细胞,产生新的癌细胞并支持瘤扩张.
科学领域:
- 在瘤学瘤学.
- 干细胞生物学 干细胞生物学
- 胃肠病学 胃肠病学
背景情况:
- 癌症干细胞假说提出,瘤是由特定的干细胞维持的.
- 这个概念仍然是科学界正在进行的研究和辩论的主题.
研究的目的:
- 提供干细胞活性在肠腺瘤,结直肠癌的前体干细胞活动的直接,功能性证据.
- 研究Lgr5表达细胞在维持腺瘤生长中的作用.
主要方法:
- 使用了肠腺瘤的小鼠模型.
- 使用多颜色的Cre-reporter R26R-Confetti进行了血统追踪.
- 在腺瘤内识别和特征Lgr5阳性细胞.
主要成果:
- 证明Lgr5阳性细胞在肠腺瘤中具有干细胞活性.
- 表明Lgr5(+) 细胞占腺瘤细胞的5-10%,并且可以自我更新.
- 证实Lgr5(+) 细胞产生所有腺瘤细胞类型,促进瘤生长.
- 观察到Lgr5(+) 细胞与Paneth细胞混合在一起,模仿正常的密码结构.
结论:
- 提供了支持肠道腺瘤癌干细胞假设的功能证据.
- 确定了Lgr5表达细胞作为肠腺瘤生长和维持的关键驱动因素.
- 突出了腺瘤和正常密码利基架构之间的相似之处.
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