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Liver Cell Polyploidization: A Pivotal Role for Binuclear Hepatocytes
Open accessAbstract
Polyploidy is a general physiological process indicative of terminal differentiation. During liver growth, this process generates the appearance of tetraploid (4n) and octoploid (8n) hepatocytes with one or two nuclei. The onset of polyploidy in the liver has been recognized for quite some time; however, the cellular mechanisms that govern it remain unknown. In this report, we observed the sequential appearance during liver growth of binuclear diploid (2 x 2n) and mononuclear 4n hepatocytes from a diploid hepatocyte population. To identify the cell cycle modifications involved in hepatocyte polyploidization, mitosis was then monitored in primary cultures of rat hepatocytes. Twenty percent of mononuclear 2n hepatocytes failed to undergo cytokinesis with no observable contractile movement of the ring. This process led to the formation of binuclear 2 x 2n hepatocytes. This tetraploid condition following cleavage failure did not activate the p53-dependent checkpoint in G1. In fact, binuclear hepatocytes were able to proceed through S phase, and the formation of a bipolar spindle during mitosis constituted the key step leading to the genesis of two mononuclear 4n hepatocytes. Finally, we studied the duplication and clustering of centrosomes in the binuclear hepatocyte. These cells exhibited two centrosomes in G1 that were duplicated during S phase and then clustered by pairs at opposite poles of the cell during metaphase. This event led only to mononuclear 4n progeny and maintaine…
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“Expression of E2f7 and E2f8 is induced at the time of weaning when the tissue switches from initially containing diploid hepatocytes to becoming mostly polyploid (4, 9, 10).”
From Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade (2022) · cites this paper as [4]
In the citing paper
“In some tissues, including the liver, cells can enter S phase to duplicate their genome, but do not complete M phase, thus becoming polyploid (4–6).”
From Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade (2022) · cites this paper as [4]
In the citing paper
“Curiously, at birth, all hepatocytes are diploid, with accumulation of polyploid hepatocytes, mostly 4n and some 8n, occurring during post-natal development (further reviewed in[29], [30], [31]), until polyploid hepatocytes account for ∼90% of hepatocytes in rodent livers and 30% in human livers.[32], [33], [34], [35]”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [34]
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Metadata
- Authors
- Guidotti, J.-E., Brégerie, O., Robert, A., Debey, P., Brechot, C., & Desdouets, C.
- Affiliations
- Hôpital Necker-Enfants Malades (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Desdouets, Chantal
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-05
- Volume
- 278
- Issue
- 21
- Pages
- 19095-19101
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1979685062
- Cited by
- 315
- References
- 35
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 10 · 2023: 11 · 2022: 13 · 2021: 11 · 2020: 13 · 2019: 11 · 2018: 17 · 2017: 14 · 2016: 17 · 2015: 15 · 2014: 12 · 2013: 19 · 2012: 22
- FWCI
- 7.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- binuclear hepatocytes, liver growth, cytokinesis failure, mitosis, bipolar spindle, centrosome duplication, centrosome clustering, G1/S checkpoint, cell cycle
- MeSH terms
- Animals, Cell Division, Cell Nucleus, Cells, Cultured, DNA, Fluorescent Antibody Technique, Kinetics, Male, Microscopy, Fluorescence, Mitosis, Polyploidy, Blotting, Western, Tumor Suppressor Protein p53, G1 Phase, S Phase, Rats, Wistar, Centrosome, Microscopy, Video, Hepatocytes, Rats
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