亚皮细胞是支持肠道密室的Wnts的重要来源
Michal Shoshkes-Carmel1, Yue J Wang1, Kirk J Wangensteen1
1Department of Genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nature
|May 4, 2018
概括
亚皮细胞是产生 Wnt 蛋白质的关键细胞,对于肠道干细胞的增殖和上皮细胞的更新至关重要. 它们的功能障碍阻断了Wnt信号, 损害了组织再生.
科学领域:
- 胃肠病学
- 干细胞生物学
- 细胞信号传输
背景情况:
- 肠道上皮质等快速自我更新的组织依赖于干细胞和前代细胞.
- 这些干细胞需要来自本地利基细胞的信号进行增殖和自我更新.
- 特定的细胞和调节肠道干细胞的信号仍然不完全理解.
研究的目的:
- 确定负责向肠道干细胞提供重要信号的特定细胞.
- 阐明这些利基细胞在调节Wnt信号和肠上皮再生中的作用.
主要方法:
- 在FOXL1+三细胞中使用有条件基因切除的小鼠模型.
- 研究了在整个胃肠道形成的亚皮细胞中FOXL1的表达.
- 分析了Wnt信号,干细胞和过渡细胞扩散,以及在三细胞特异性基因切除后的上皮细胞更新.
主要成果:
- 确定FOXL1+亚皮细胞是肠干细胞Wnt蛋白的主要来源.
- 证明三细胞对Wnt连接体和抑制剂的产生进行区分,以实现局部途径的激活.
- 表明在FOXL1+三细胞中切除Porcn会迅速停止Wnt信号传递,导致干细胞增殖丧失和上皮细胞更新受损.
结论:
- 通过Wnt蛋白的产生来调节肠道干细胞的功能.
- 这些三细胞在维持肠上皮质平衡和再生方面发挥着至关重要的作用.
- 向来自三细胞的Wnt信号是肠道疾病的潜在治疗策略.
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