Hepatocyte Polyploidy: Driver or Gatekeeper of Chronic Liver Diseases

Abstract

Polyploidy, also known as whole-genome amplification, is a condition in which the organism has more than two basic sets of chromosomes. Polyploidy frequently arises during tissue development and repair, and in age-associated diseases, such as cancer. Its consequences are diverse and clearly different between systems. The liver is a particularly fascinating organ in that it can adapt its ploidy to the physiological and pathological context. Polyploid hepatocytes are characterized in terms of the number of nuclei per cell (cellular ploidy; mononucleate/binucleate hepatocytes) and the number of chromosome sets in each nucleus (nuclear ploidy; diploid, tetraploid, octoploid). The advantages and disadvantages of polyploidy in mammals are not fully understood. About 30% of the hepatocytes in the human liver are polyploid. In this review, we explore the mechanisms underlying the development of polyploid cells, our current understanding of the regulation of polyploidization during development and pathophysiology and its consequences for liver function. We will also provide data shedding light on the ways in which polyploid hepatocytes cope with centrosome amplification. Finally, we discuss recent discoveries highlighting the possible roles of liver polyploidy in protecting against tumor formation, or, conversely, contributing to liver tumorigenesis.

Molecular landscape and functional characterization of centrosome amplification in ovarian cancer

“…In addition, we included 24 normal fallopian tube (FT) samples, a spleen, and a kidney samples as negative controls. Normal liver samples were included as positive control tissues for CA, as the liver is the only organ in the human body that displays centrosome amplification in a healthy state [29][30][31] . An overview of all analysed tissue samples (n=318) is shown in Supplementary Table 1.…”

“…In addition to the 287 tumour samples, we also included 24 normal fallopian tube (FT) samples, one normal spleen, one normal kidney and five normal liver samples. Importantly, the liver is the only organ in the human body that displays centrosome amplification in a healthy state, likely caused by multi-nucleation and polyploidisation during tissue development [29][30][31] . Liver tissues were therefore used as positive controls in this study.…”

The Controversial Role of Polyploidy in Hepatocellular Carcinoma

“…Some latest studies have elegantly described the factors affecting cytokinesis and the molecular mechanism of cytokinesis failure, playing a guiding role in the subsequent research. Margall-Ducos et al 31,32 showed that cytokinesis is interrupted by impaired reorganization of the actin cytoskeleton at the division plane during the anaphase-telophase transition, resulting in loss of cell extension. Meanwhile, astral microtubules failed to contact the equatorial cortex and to deliver their molecular signal, which prevents activation of the RhoA pathway and leads to the generation of binucleate progenies.…”

Implications of Polyploidy and Ploidy Alterations in Hepatocytes in Liver Injuries and Cancers

“…Although the mechanism underlying the regulation of the ploidy of hepatocytes and its effects on the pathophysiology of the liver are unclear, accumulating evidence indicates that polyploidy and alterations in the ploidy in hepatocytes influence liver homeostasis and diseases both positively and negatively. Whereas some reviews have outlined the advantages and disadvantages of polyploidy in health and disease in various organs [ 3 , 4 ], few papers have highlighted updated discussions about hepatocyte ploidy, especially ploidy alterations, and liver diseases [ 5 , 6 , 7 ]. This review discusses the significance of hepatocyte ploidy, with respect to physiological liver function, liver injury, and cancer.…”