Children's Research Institute, Departments of Pediatrics and Internal Medicine, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Quantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science. 2021 Feb 26;371(6532). doi: 10.1126/science.abb1625.
The liver is organized into zones in which hepatocytes express different metabolic enzymes. The cells most responsible for liver repopulation and regeneration remain undefined, because fate mapping has only been performed on a few hepatocyte subsets. Here, 14 murine fate-mapping strains were used to systematically compare distinct subsets of hepatocytes. During homeostasis, cells from both periportal zone 1 and pericentral zone 3 contracted in number, whereas cells from midlobular zone 2 expanded in number. Cells within zone 2, which are sheltered from common injuries, also contributed to regeneration after pericentral and periportal injuries. Repopulation from zone 2 was driven by the insulin-like growth factor binding protein 2-mechanistic target of rapamycin-cyclin D1 (IGFBP2-mTOR-CCND1) axis. Therefore, different regions of the lobule exhibit differences in their contribution to hepatocyte turnover, and zone 2 is an important source of new hepatocytes during homeostasis and regeneration.
肝脏组织成区，其中肝细胞表达不同的代谢酶。负责肝再殖和再生的细胞仍未定义，因为命运映射仅在少数肝细胞亚群上进行。在这里，使用了 14 种鼠类命运映射株系来系统地比较不同的肝细胞亚群。在稳态下，来自门脉周区 1 和中央区 3 的细胞数量减少，而来自中肝区 2 的细胞数量增加。位于免受常见损伤庇护的区 2 的细胞也有助于中央区和门脉周损伤后的再生。来自区 2 的再殖是由胰岛素样生长因子结合蛋白 2-雷帕霉素靶蛋白-细胞周期蛋白 D1 (IGFBP2-mTOR-CCND1) 轴驱动的。因此，小叶的不同区域在其对肝细胞更新的贡献上存在差异，区 2 是稳态和再生期间新肝细胞的重要来源。
