Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair

Abstract

Zoning in on liver growth For organ homeostasis or regrowth after injury or disease, one or more stem cell populations is needed to rebuild lost tissue. There is considerable debate about the source of new cells in the liver. Two groups now identify the source of new hepatocytes (see the Perspective by Andersson). Although the liver may seem to lack major variation across its structure, its lobule is organized into concentric zones where hepatocytes express different metabolic enzymes. Wei et al. sought to systematically define the source of new liver cells by comparing 14 fate-mapping mice that label different liver cell types. They found that different regions of the liver lobule exhibit differences in hepatocyte turnover, with zone 2 representing a primary source of new hepatocytes during homeostasis and regeneration. Similarly, He et al. designed a genetic approach to record cell proliferation in vivo with high spatial and temporal resolution to enable continuous recording of proliferative events of any specific cell type at the whole-cell population level. Using this method, they identified zone 2 as having the highest proliferative activity and contributing the most to liver regrowth. These findings have implications for the cellular basis of chronic disease pathogenesis, cancer development, and regenerative medicine strategies. Science , this issue p. eabb1625 , p. eabc4346 ; see also p. 887