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单细胞激活屏幕识别了具有区域分辨率的肝成熟调节器.

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概括

研究人员确定了控制肝细胞成熟的重点转录因子Nr1i3和Nfix. 这一发现有助于理解器官发育和改善实验室培养的肝细胞.

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科学领域:

  • 发育生物学是发展生物学.
  • 肝病学 肝病学是一种肝病学.
  • 基因调节 基因调节

背景情况:

  • 胚胎肝细胞的成熟涉及复杂的基因调节网络 (GRN) 的重新连接.
  • 在体外获得完全成熟的功能性肝细胞仍然是一个重大挑战.
  • 晚期肝脏发育的关键转录调节者还没有得到很好的定义.

研究的目的:

  • 为了确定控制胚胎肝细胞晚期成熟的新型转录调节剂.
  • 了解肝脏发育过程中GRN重新连接的机制.
  • 为了增强体外衍生肝细胞的功能.

主要方法:

  • 为小鼠胚胎肝细胞创建一个发育参考地图.
  • 使用dCas9激活屏幕与单细胞转录组学相结合.
  • 排列了晚期发病的转录调节器对肝细胞基因表达的影响.

主要成果:

  • 鉴定Nr1i3作为一个强大的诱导器的周围中心代谢基因.
  • 确定了Nfix作为胚胎和周边基因签名的关键抑制剂.
  • 补充肝脏区域信号与Nr1i3和Nfix增强的中心周代谢基因表达.

结论:

  • Nr1i3和Nfix在编排肝细胞成熟和区分方面发挥着至关重要的作用.
  • 使用已识别的调节剂的微环境向方法可以改善体外细胞功能.
  • 该研究提供了对器官成熟调节机制和细胞治疗策略的见解.