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Semin Liver Dis 2023; 43(04): 460-471
DOI: 10.1055/a-2211-2144
DOI: 10.1055/a-2211-2144
Review Article
The Ploidy State as a Determinant of Hepatocyte Proliferation
Funding This work was supported by grants to A.W.D. from the National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases; U.S. Department of Health and Human Services) (R01 DK103645) and the Commonwealth of Pennsylvania. S.R.W. was supported by the National Institute of Biomedical Imaging and Bioengineering. NIBIB training grant, T32 EB001026, entitled “Cellular Approaches to Tissue Engineering and Regeneration.”
Abstract
The liver's unique chromosomal variations, including polyploidy and aneuploidy, influence hepatocyte identity and function. Among the most well-studied mammalian polyploid cells, hepatocytes exhibit a dynamic interplay between diploid and polyploid states. The ploidy state is dynamic as hepatocytes move through the “ploidy conveyor,” undergoing ploidy reversal and re-polyploidization during proliferation. Both diploid and polyploid hepatocytes actively contribute to proliferation, with diploids demonstrating an enhanced proliferative capacity. This enhanced potential positions diploid hepatocytes as primary drivers of liver proliferation in multiple contexts, including homeostasis, regeneration and repopulation, compensatory proliferation following injury, and oncogenic proliferation. This review discusses the influence of ploidy variations on cellular activity. It presents a model for ploidy-associated hepatocyte proliferation, offering a deeper understanding of liver health and disease with the potential to uncover novel treatment approaches.
Publication History
Accepted Manuscript online:
15 November 2023
Article published online:
15 December 2023
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