Cited by 315Liver physiology and pathologyMicrotubule and mitosis dynamicsChromosomal and Genetic Variations

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Liver Cell Polyploidization: A Pivotal Role for Binuclear Hepatocytes

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Guidotti, Jacques-Emmanuel, Brégerie, Olivier, Robert, Aude, Debey, Pascale, Brechot, Christian, Desdouets, Chantal·2003·Journal of Biological Chemistry

DOI 10.1074/jbc.m300982200

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Abstract

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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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
ORCID: Guidotti, Jacques-Emmanuel
Robert, Aude
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)
DOI: 10.1074/jbc.m300982200
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6354 d)
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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Liver Cell Polyploidization: A Pivotal Role for Binuclear Hepatocytes

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