在人类慢性肝病中获得上皮质可塑性
Christopher Gribben1,2, Vasileios Galanakis1,2,3, Alexander Calderwood1
1Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Nature
|May 22, 2024
概括
人类肝脏在慢性疾病中的再生是复杂的. 这项研究揭示了由PI3K-AKT-mTOR途径驱动的肝细胞和胆细胞之间的细胞可塑性和转差,为肝脏疾病提供了新的治疗点.
科学领域:
- 肝病学和再生医学
- 分子和细胞生物学
- 疾病病理学
背景情况:
- 慢性疾病中成年人器官的组织再生尚不清楚.
- 虽然动物模型显示再生,但人类的验证是有限的.
- 在急性损伤后肝脏的再生能力是已知的,但在慢性,复发性损伤期间的再生能力不太清楚.
研究的目的:
- 研究人类慢性疾病中的肝脏再生机制.
- 在代谢功能障碍相关的脂肪性肝病进展过程中创建肝脏的细胞和结构图.
- 在人类肝脏疾病中识别细胞可塑性和转化事件.
主要方法:
- 在47个人类肝脏活检中进行单核RNA测序 (snRNA-seq).
- 分析肝脏结构的高级3D成像.
- 使用胆细胞器官的功能验证.
主要成果:
- 建立了不同代谢功能失调相关的脂肪性肝病的不同阶段的肝细胞图.
- 观察到肝细胞区分的丧失和明显的胆管树重组.
- 肝细胞和胆细胞之间未发现的转差,独立于干细胞或前代细胞激活.
- 确定PI3K-AKT-mTOR途径在细胞可塑性中的作用,与胰岛素信号相关.
结论:
- 慢性肝损伤会导致人体器官的细胞可塑性.
- 肝细胞和胆血管细胞之间的转差是人类肝病的关键再生机制.
- 了解这些机制可能会导致慢性肝病的新疗法.
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