Yang Li, Wang Xin, Zheng Jia-Xi, Xu Zi-Ran, Li Lin-Chen, Xiong Yu-Long, Zhou Bi-Chen, Gao Jie, Xu Cheng-Ran
Department of Human Anatomy, Histology, and Embryology, School of Basic Medical Sciences, Peking University, Beijing 100191, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
School of Life Sciences, Peking University, Beijing 100871, China.
Dev Cell. 2023 Oct 9;58(19):1996-2010.e6. doi: 10.1016/j.devcel.2023.07.006. Epub 2023 Aug 8.
Hepatocytes, the liver's predominant cells, perform numerous essential biological functions. However, crucial events and regulators during hepatocyte maturation require in-depth investigation. In this study, we performed single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) to explore the precise hepatocyte development process in mice. We defined three maturation stages of postnatal hepatocytes, each of which establishes specific metabolic functions and exhibits distinct proliferation rates. Hepatic zonation is gradually formed during hepatocyte maturation. Hepatocytes or their nuclei with distinct ploidies exhibit zonation preferences in distribution and asynchrony in maturation. Moreover, by combining gene regulatory network analysis with in vivo genetic manipulation, we identified critical maturation- and zonation-related transcription factors. This study not only delineates the comprehensive transcriptomic profiles of hepatocyte maturation but also presents a paradigm to identify genes that function in the development of hepatocyte maturation and zonation by combining genetic manipulation and measurement of coordinates in a single-cell developmental trajectory.
肝细胞是肝脏的主要细胞，执行众多重要的生物学功能。然而，肝细胞成熟过程中的关键事件和调节因子需要深入研究。在本研究中，我们进行了单细胞RNA测序（scRNA-seq）和单核RNA测序（snRNA-seq），以探索小鼠肝细胞的精确发育过程。我们定义了出生后肝细胞的三个成熟阶段，每个阶段都建立了特定的代谢功能并表现出不同的增殖率。肝小叶在肝细胞成熟过程中逐渐形成。具有不同倍性的肝细胞或其细胞核在分布上表现出小叶偏好，在成熟过程中表现出不同步性。此外，通过将基因调控网络分析与体内基因操作相结合，我们鉴定出了与成熟和小叶相关的关键转录因子。本研究不仅描绘了肝细胞成熟的全面转录组图谱，还提供了一个范例，即通过结合基因操作和单细胞发育轨迹中的坐标测量来鉴定在肝细胞成熟和小叶发育中起作用的基因。
