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Summary
In humans, the liver is the most regenerative solid organ, able to regrow to normal size after removal of up to 90% of the liver volume (1, 2). The liver is also distinct because it scales with body size, a characteristic that has been attributed to a “hepatostat” that adjusts liver size to the needs of the body (3). Identifying the cells contributing to liver homeostasis and repair could lead to therapies that can activate specific cellular compartments responsible for regeneration. On pages 906 and 905 of this issue, Wei et al. (4) and He et al. (5), respectively, find that, in mice, a subset of cells in a particular region of the liver, called midlobular zone 2, are the major contributors to hepatocyte proliferation during homeostasis and identify other hepatocyte subsets that contribute to regeneration after damage. This raises questions regarding the mechanisms that induce hepatocyte proliferation and the zonal division of labor with respect to the hepatostat.
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