Hepatocytes Polyploidization and Cell Cycle Control in Liver Physiopathology
Figure 1
Hepatocytes polyploidization during development and in challenging circumstances: (A) polyploidization during postnatal liver growth. Hepatocytes in newborn are exclusively diploid (mononucleated 2n). At the weaning period, diploid hepatocytes can engage either into normal cell division cycle (black arrow) giving rise to two diploid hepatocytes or follow an adaptive cell cycle with cytokinesis failure (red arrow) giving rise to one binucleated tetraploid hepatocyte. By this process, progressive polyploidization takes place in the liver parenchyma and tetraploid and octoploid cell classes with one or two nuclei are formed. (B) Ploidy modification during physiopathological processes in adult liver. In adult, liver modulates its ploidy in response to different signals. Liver regeneration induced by partial hepatectomy leads to the disappearance of binucleated hepatocytes and the formation of mononucleated tetraploid and octoploid hepatocytes or even 16n contingent. DNA synthesis induced by chemicals or following oxidative damage and metabolic overload (copper/iron) is associated with a pronounced increase in the proportion of polyploid hepatocytes. Furthermore, in response to different unknown signals, hepatocytes can both increase (bipolar mitosis followed by cytokinesis failure) or decrease their ploidy (multipolar mitosis). In that case, near-diploid/near-polyploid contingents will be generated, leading to the genesis of genetically distinct daughter cells; black arrow: complete cytokinesis, red arrow: cytokinesis failure.
