Clinics and Research in Hepatology and Gastroenterology
Mini reviewPolyploidy and liver proliferation
Section snippets
Abbreviations
- SAC
spindle assembly checkpoint
- APC
adenomatous polyposis coliAFM
- PH
partial hepatectomy
- LEC
long Evans Cinnamon rats
- WD
Wilson's disease
Mechanisms generating polyploid cells
One fascinating question is how diploid organisms develop polyploid cells. In a physiological or pathological state, polyploid cells can arise by any of at least five main mechanisms: cell fusion, endoreplication, endomitosis, mitotic slippage and cytokinesis failure (Fig. 1). Cell fusions are important in several physiological processes, including fertilization, development (osteoclasts) and tissue repair (skeletal muscle cells) [9], [10]. Infection with many viruses can also induce cell
Polyploidy and liver growth
Hepatic development is an extended process that continues through early post-natal life. In rat liver, through E14, most hepatoblasts are bipotent with the ability to differentiate into hepatocytes or into biliary cells; however, by E15 most hepatoblasts are committed to the hepatocyte lineage [23], [24]. During the remaining period of gestation and the first four post-natal weeks, hepatoblasts acquire functions of differentiated hepatocytes. In parallel with this process, there is a
Polyploidy in regenerating liver and during pathological states
The adult liver retains a high proliferative capacity. It responds to tissue injuries such as PH, toxin and drug-induced liver disease as well as administration of specific growth factor by priming quiescent hepatocytes [42]. During liver regeneration, after PH, quiescent hepatocytes undergo one or two rounds of replication to restore the liver mass by a process of compensatory hyperplasia. Many studies have shown that during this process hepatic polyploidy is modified [2], [43], [44], [45],
Conclusion and perspectives
Although hepatic polyploidisation has been shown to be associated with physiologic and pathologic events, our understanding of the consequences for hepatocytes is quite limited. Various possibilities can be suggested: (i) polyploidy may protect hepatocytes from genotoxic damage by increasing their gene copy number; this might be especially important for the liver that has a primary function in metabolizing and eliminating toxic compounds. (ii) The polyploidy process may be link to energy
Disclosure of interest
The authors declare that they have no conflicts of interest concerning this article.
Acknowledgements
We thank the editor for inviting this mini review. G. Gentric is a recipient of DIM RĆ©gion Ile de France āCardio-vasculaire DiabĆØte ObĆ©sitĆ©ā. This study was supported by grants from Institut National de la SantĆ© et de la Recherche MĆ©dicale (Inserm), ANR-FORM-090601-01-01, by INCa-CHC (2009-1-CHC-03-Inserm).
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2022, Pharmacology and TherapeuticsCitation Excerpt :While polyploid hepatocytes reduce their proliferation capacity with aging and pathological processes, they act as growth inhibitors to limit the proliferation of most hepatocytes, and senescent polyploid hepatocytes can be regenerated through ploidy reversal. When hepatocellular carcinoma occurs, it is mainly driven by diploid hepatocytes, so induction of polyploidy may be a potential strategy for cancer treatment(F. Chen et al., 2020; Gentric, Celton-Morizur, & Desdouets, 2012; Gupta, 2000; M. J. Wang et al., 2017; Wilkinson et al., 2019). Therefore, understanding the mechanism of liver regeneration is crucial for the treatment of various liver diseases.
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2021, Cellular and Molecular Gastroenterology and HepatologyIn Vivo Lineage Tracing of Polyploid Hepatocytes Reveals Extensive Proliferation during Liver Regeneration
2020, Cell Stem CellCitation Excerpt :This multipolar reductive mitosis might enhance effective organ regeneration by generating more than two cells in one cell division. On the other hand, some studies have shown that polyploid hepatocytes exhibit senescence-associated changes following one or two rounds of cell division (Gentric et al., 2012; Sigal et al., 1999). Additionally, it has been suggested that diploid hepatocytes adjacent to the central vein of the liver lobule act as stem cells during homeostasis and injury response (Wang et al., 2015).
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2018, Food Science and Human WellnessCitation Excerpt :Nevertheless, certain organisms can undergo successive rounds of genome duplication in the absence of cytokinesis to acquire a polyploid status that can involve the whole organism or just specific tissues and organs (Edgar et al., 2014; Fox and Duronio, 2013; Schoenfelder and Fox, 2015). Among mammals, including humans, polyploidy is particularly relevant in the liver hepatocytes, megakaryocytes, and placental giant trophoblast cells, although it also takes place in the heart and muscle (Gentric et al., 2012; Hannibal et al., 2014). In the liver, the percentage of polyploid hepatocytes ranges from 80% to 90% in rats, to 30% in humans, and to close to 50% in mice (Celton-Morizur et al., 2010; Duncan et al., 2010).