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.

肝脏被组织成肝细胞表达不同代谢酶的区域。最负责肝脏再增殖和再生的细胞仍未确定，因为仅对少数肝细胞亚群进行了命运定位。在这里，使用 14 种小鼠命运映射品系来系统地比较不同的肝细胞亚群。在稳态期间，来自门静脉区 1 和中心区 3 的细胞数量收缩，而小叶中区 2 的细胞数量增加。区域 2 内的细胞不受常见损伤的影响，也有助于中心周围和门静脉周围损伤后的再生。区域 2 的重新增殖是由胰岛素样生长因子结合蛋白 2-雷帕霉素-细胞周期蛋白 D1（IGFBP2-mTOR-CCN​​D1）轴的机制靶点驱动的。所以，