Liver homeostasis is maintained by midlobular zone 2 hepatocytes

Yonglong Wei, Yunguan G. Wang, Yuemeng Jia, Lin Li, Jung Yoon, Shuyuan Zhang, Zixi Wang, Yu Zhang, Min Zhu, Tripti Sharma, Yu Hsuan Lin, Meng Hsiung Hsieh, Jeffrey H. Albrecht, Phuong T. Le, Clifford J. Rosen, Tao Wang, Hao Zhu

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102 Scopus citations


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.

Original languageEnglish (US)
Article numberabb1625
Issue number6532
StatePublished - Feb 26 2021

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