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…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Expression of E2f7 and E2f8 is induced at weaning when the liver switches from diploid to polyploid.
“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 some tissues including liver, cells can enter S phase but not complete M phase, becoming polyploid.
“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]
At birth, all hepatocytes are diploid, with accumulation of polyploid hepatocytes, mostly 4n and some 8n, occurring during post-natal development until polyploid hepatocytes account for ∼90% of hepatocytes in rodent livers and 30% in human livers.
“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]
Cites
Meraldi, P., Honda, R., & Nigg, E. A. (2002) · The EMBO Journal · doi:10.1093/emboj/21.4.483 · Cited by 659 · see citing works
Ploidy Regulation of Gene Expression
Galitski, T., Saldanha, A. J., Styles, C. A., Lander, E. S., & Fink, G. R. (1999) · Science · doi:10.1126/science.285.5425.251 · Cited by 633 · see citing works
PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone
Mollinari, C., Kleman, J.-P., Jiang, W. B., Schoehn, G., Hunter, T. R., & Margolis, R. L. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200111052 · Cited by 468 · see citing works
Tetraploid State Induces p53-dependent Arrest of Nontransformed Mammalian Cells in G1
Andreassen, P. R., Lohez, O. D., Lacroix, F., & Margolis, R. L. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.5.1315 · Cited by 429 · see citing works
Role of citron kinase as a target of the small GTPase Rho in cytokinesis
Madaule, P., Eda, M., Watanabe, N., Fujisawa, K., Matsuoka, T., Bito, H., Ishizaki, T., & Narumiya, S. (1998) · Nature · doi:10.1038/28873 · Cited by 402 · see citing works
AIM‐1: a mammalian midbody‐associated protein required for cytokinesis
Terada, Y., Tatsuka, M., Suzuki, F., Yasuda, Y., Fujita, S., & Otsu, M. (1998) · The EMBO Journal · doi:10.1093/emboj/17.3.667 · Cited by 395 · see citing works
Nislow, C., Lombillo, V. A., Kuriyama, R., & McIntosh, J. R. (1992) · Nature · doi:10.1038/359543a0 · Cited by 357 · see citing works
Plk Is an M-Phase-Specific Protein Kinase and Interacts with a Kinesin-Like Protein, CHO1/MKLP-1
Lee, K. S., Yuan, Y.-L. O., Kuriyama, R., & Erikson, R. L. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.12.7143 · Cited by 268 · see citing works
Roads to polyploidy: The megakaryocyte example
Ravid, K., Lü, J., Zimmet, J. M., & Jones, M. R. (2001) · Journal of Cellular Physiology · doi:10.1002/jcp.10035 · Cited by 267 · see citing works
The Centrosomal Protein C-Nap1 Is Required for Cell Cycle–Regulated Centrosome Cohesion
Mayor, T., Stierhof, Y., Tanaka, K., Fry, A. M., & Nigg, E. A. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.4.837 · Cited by 237 · see citing works
Human Survivin Is a Kinetochore-Associated Passenger Protein
Skoufias, D. A., Mollinari, C., Lacroix, F., & Margolis, R. L. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.7.1575 · Cited by 236 · see citing works
Wu, H., Wade, M., Krall, L., Grisham, J., Xiong, Y., & Van Dyke, T. (1996) · Genes & Development · doi:10.1101/gad.10.3.245 · Cited by 234 · see citing works
Borel, F., Lohez, O. D., Lacroix, F., & Margolis, R. L. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.152205299 · Cited by 193 · see citing works
MgcRacGAP Is Involved in Cytokinesis through Associating with Mitotic Spindle and Midbody
Hirose, K., Kawashima, T., Iwamoto, I., Nosaka, T., & Kitamura, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007252200 · Cited by 191 · see citing works
Human hepatocyte polyploidization kinetics in the course of life cycle
Kudryavtsev, B. N., Kudryavtseva, M. V., Sakuta, G. A., & Stein, G. I. (1993) · Virchows Archiv B Cell Pathology Including Molecular Pathology · doi:10.1007/bf02915139 · Cited by 170 · see citing works
Mackay, A. M., Ainsztein, A. M., Eckley, D. M., & Earnshaw, W. C. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.140.5.991 · Cited by 150 · see citing works
Binucleation in mammalian liver
Wheatley, D. N. (1972) · Experimental Cell Research · doi:10.1016/0014-4827(72)90401-6 · Cited by 124 · see citing works
Lange, B. M. H. (2002) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(01)00291-5 · Cited by 97 · see citing works
Emergence of a population of small, diploid hepatocytes during hepatocarcinogenesis
Schwarze, P. E., Pettersen, E. O., Shoaib, M. C., & Seglen, P. O. (1984) · Carcinogenesis · doi:10.1093/carcin/5.10.1267 · Cited by 95 · see citing works
Evidence for a terminal differentiation process in the rat liver
Sigal, S. H., Gupta, S. K., Gebhard, D. F., Holst, P. A., Neufeld, D. S., & Reid, L. M. (1995) · Differentiation · doi:10.1046/j.1432-0436.1995.5910035.x · Cited by 90 · see citing works
DNA ploidy and autophagic protein degradation as determinants of hepatocellular growth and survival
Seglen, P. O. (1997) · Cell Biology and Toxicology · doi:10.1023/a:1007487425047 · Cited by 89 · see citing works
Bellamy, C. O. C., Clarke, A. R., Wyllie, A. H., & Harrison, D. J. (1997) · The FASEB Journal · doi:10.1096/fasebj.11.7.9212083 · Cited by 84 · see citing works
Minamishima, Y. A., Nakayama, K., & Nakayama, K. (2002) · PubMed · Cited by 76 · see citing works
Sæter, G., Schwarze, P. E., Nesland, J. M., Juul, N., Pettersen, E. O., & Seglen, P. O. (1988) · Carcinogenesis · doi:10.1093/carcin/9.6.939 · Cited by 76 · see citing works
Núñez, F., Chipchase, M. D., Clarke, A. R., & Melton, D. W. (2000) · The FASEB Journal · doi:10.1096/fasebj.14.9.1073 · Cited by 68 · see citing works
Ploidy-Dependent Growth and Binucleation in Cultured Rat Hepatocytes
Mossin, L., Blankson, H., Huitfeldt, H. S., & Seglen, P. O. (1994) · Experimental Cell Research · doi:10.1006/excr.1994.1293 · Cited by 62 · see citing works
Citron Kinase Is a Cell Cycle-dependent, Nuclear Protein Required for G2/M Transition of Hepatocytes
Liu, H., Cunto, F. D., Imarisio, S., & Reid, L. M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210391200 · Cited by 54 · see citing works
Martineau-Thuillier, S. X. E. P., Andreassen, P. R., & Margolis, R. L. (1998) · Chromosoma · doi:10.1007/s004120050330 · Cited by 52 · see citing works
Martin, N. C., McCullough, C. T., Bush, P. G., Sharp, L., Hall, A. C., & Harrison, D. J. (2002) · Journal of Cellular Physiology · doi:10.1002/jcp.10057 · Cited by 47 · see citing works
Vav3 is regulated during the cell cycle and effects cell division
Fujikawa, K., Inoue, Y., Sakai, M., Koyama, Y., Nishi, S., Funada, R., Alt, F. W., & Swat, W. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052715699 · Cited by 41 · see citing works
Control of mouse hepatocyte proliferation and ploidy by p53 and p53ser246 mutation in vivo
Yin, L., Ghebranious, N., Chakraborty, S., Sheehan, C. E., Ilic, Z., & Sell, S. (1998) · Hepatology · doi:10.1002/hep.510270113 · Cited by 37 · see citing works
McIntyre, M., Desdouets, C., Sénamaud‐Beaufort, C., Laurent‐Winter, C., Lamas, E., & Bréchot, C. (1999) · Oncogene · doi:10.1038/sj.onc.1202815 · Cited by 25 · see citing works
Self-citationNadal, C., & Zajdela, F. (1967) · Experimental Cell Research · doi:10.1016/0014-4827(67)90318-7 · Cited by 15 · see citing works
Evolutive changes of ploidy and polynucleation in adult rat hepatocytes in culture.
Mj, G.-L., Barberá, E., Gil, R., & Báguena, J. (1981) · PubMed · Cited by 11 · see citing works
Chassoux, D. M., Franchi, J., Cao, T. T., & Debey, P. (1999) · PubMed · Cited by 10 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
From polyploidy to aneuploidy, genome instability and cancer
Štorchová, Z., & Pellman, D. S. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1276 · Cited by 810 · see citing works
Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver
Wang, B., Zhao, L., Fish, M., Logan, C. Y., & Nusse, R. (2015) · Nature · doi:10.1038/nature14863 · Cited by 674 · see citing works
Tetraploidy, aneuploidy and cancer
Ganem, N. J., Storchova, Z., & Pellman, D. (2007) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2007.02.011 · Cited by 668 · see citing works
Pan, C., Kumar, C., Bohl, S., Klingmueller, U., & Mann, M. (2009) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m800258-mcp200 · Cited by 561 · see citing works
“Most primary hepatocytes are binuclear (34).”
Weaver, B. A. A., & Cleveland, D. W. (2006) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2006.10.002 · Cited by 560 · see citing works
The ploidy conveyor of mature hepatocytes as a source of genetic variation
Duncan, A. W., Taylor, M. H., Hickey, R. D., Hanlon Newell, A. E., Lenzi, M. L., Olson, S. B., Finegold, M. J., & Grompe, M. (2010) · Nature · doi:10.1038/nature09414 · Cited by 525 · see citing works
Hypertrophy and Unconventional Cell Division of Hepatocytes Underlie Liver Regeneration
Miyaoka, Y., Ebato, K., Kato, H., Arakawa, S., Shimizu, S., & Miyajima, A. (2012) · Current Biology · doi:10.1016/j.cub.2012.05.016 · Cited by 461 · see citing works
Cardiac Stem Cells and Mechanisms of Myocardial Regeneration
Leri, A., Kajstura, J., & Anversa, P. (2005) · Physiological Reviews · doi:10.1152/physrev.00013.2005 · Cited by 445 · see citing works
The Causes and Consequences of Polyploidy in Normal Development and Cancer
Davoli, T., & de Lange, T. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154234 · Cited by 432 · see citing works
Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload
Niederkofler, V. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25683 · Cited by 368 · see citing works
Genome-wide genetic analysis of polyploidy in yeast
Štorchová, Z., Breneman, A., Cande, J., Dunn, J. G., Burbank, K. S., O'Toole, E. T., & Pellman, D. S. (2006) · Nature · doi:10.1038/nature05178 · Cited by 360 · see citing works
The consequences of tetraploidy and aneuploidy
Storchova, Z., & Kuffer, C. (2008) · Journal of Cell Science · doi:10.1242/jcs.039537 · Cited by 363 · see citing works
Single cell sequencing reveals low levels of aneuploidy across mammalian tissues
Knouse, K. A., Wu, J., Whittaker, C. A., & Amon, A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1415287111 · Cited by 314 · see citing works
Artegiani, B., Hendriks, D. F. G., Beumer, J., Kok, R. N. U., Zheng, X., Joore, I. P., Lopes, S. M. C. D. S., van Zon, J. S., Tans, S. J., & Clevers, H. C. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0472-5 · Cited by 302 · see citing works
Apoptosis and genomic instability
Zhivotovsky, B., & Kroemer, G. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1443 · Cited by 302 · see citing works
Cytokinesis defects and cancer
Lens, S. M. A., & Medema, R. H. (2018) · Nature reviews. Cancer · doi:10.1038/s41568-018-0084-6 · Cited by 266 · see citing works
Comparative regenerative mechanisms across different mammalian tissues
Iismaa, S. E., Kaidonis, X., Nicks, A. M., Bogush, N., Kikuchi, K., Naqvi, N., Harvey, R. P., Husain, A., & Graham, R. M. (2018) · npj Regenerative Medicine · doi:10.1038/s41536-018-0044-5 · Cited by 256 · see citing works
Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease
Gentric, G., Maillet, V., Paradis, V., Couton, D., L’Hermitte, A., Panasyuk, G., Fromenty, B., Celton-Morizur, S., & Desdouets, C. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73957 · Cited by 240 · see citing works
Self-citationThe cell biology of the hepatocyte: A membrane trafficking machine
Schulze, R. J., Schott, M. B., Casey, C. A., Tuma, P. L., & McNiven, M. A. (2019) · The Journal of Cell Biology · doi:10.1083/jcb.201903090 · Cited by 246 · see citing works
van Dijk, M., Mulders, J., Poutsma, A., Könst, A. A. M., Lachmeijer, A. M. A., Dekker, G., Blankenstein, M. A., & Oudejans, C. B. M. (2005) · Nature Genetics · doi:10.1038/ng1541 · Cited by 237 · see citing works
Stéphenne, X., Najimi, M., Sibille, C., Nassogne, M., Smets, F. N., & Sokal, E. M. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.01.008 · Cited by 212 · see citing works
Zhao, H., Li, Y., He, L., Pu, W., Yu, W., Li, Y., Wu, Y., Xu, C., Wei, Y., Ding, Q., et al. (2019) · Circulation · doi:10.1161/circulationaha.119.042476 · Cited by 212 · see citing works
Lack of p21 expression links cell cycle control and appendage regeneration in mice
Bedelbaeva, K., Snyder, A., Gourevitch, D., Clark, L., Zhang, X.-M., Leferovich, J., Cheverud, J. M., Lieberman, P., & Heber-Katz, E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000830107 · Cited by 207 · see citing works
Frequent Aneuploidy Among Normal Human Hepatocytes
Duncan, A. W., Hanlon Newell, A. E., Smith, L., Wilson, E. M., Olson, S. B., Thayer, M. J., Strom, S. C., & Grompe, M. (2012) · Gastroenterology · doi:10.1053/j.gastro.2011.10.029 · Cited by 197 · see citing works
Matsumoto, T., Wakefield, L., Tarlow, B. D., & Grompe, M. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2019.11.014 · Cited by 194 · see citing works
Skp2-dependent degradation of p27kip1 is essential for cell cycle progressionPreprint
Kossatz-Boehlert, U., Dietrich, N., Zender, L., Buer, J., Manns, M. P., & Malek, N. P. (2004) · Genes & Development · doi:10.1101/gad.321004 · Cited by 194 · see citing works
Centrosomes and cancer: how cancer cells divide with too many centrosomes
Godinho, S. A., Kwon, M., & Pellman, D. S. (2009) · Cancer and Metastasis Reviews · doi:10.1007/s10555-008-9163-6 · Cited by 193 · see citing works
Polyploidization in Liver Tissue
Gentric, G., & Desdouets, C. (2014) · The American Journal of Pathology · doi:10.1016/j.ajpath.2013.06.035 · Cited by 192 · see citing works
Self-citationDerks, W. J. A., & Bergmann, O. (2020) · Circulation Research · doi:10.1161/circresaha.119.315408 · Cited by 188 · see citing works
Polyploidy in liver development, homeostasis and disease
Donne, R., Saroul-Aïnama, M., Cordier, P., Celton-Morizur, S., & Desdouets, C. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0284-x · Cited by 188 · see citing works
Self-citationPATERSON, A., Chapman, B., Kissinger, J. C., Bowers, J., Feltus, F. A., & Estill, J. C. (2006) · Trends in Genetics · doi:10.1016/j.tig.2006.09.003 · Cited by 186 · see citing works
Aneuploidy as a mechanism for stress-induced liver adaptation
Duncan, A. W., Newell, A. E. H., Bi, W., Finegold, M. J., Olson, S. B., Beaudet, A. L., & Grompe, M. (2012) · Journal of Clinical Investigation · doi:10.1172/jci64026 · Cited by 185 · see citing works
Aneuploidy, polyploidy and ploidy reversal in the liver.
Duncan, A. (2013) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2013.01.003 · Cited by 172 · see citing works
Identification of Griseofulvin as an Inhibitor of Centrosomal Clustering in a Phenotype-Based Screen
Rebacz, B., Larsen, T. O., Clausen, M. H., Rønnest, M. H., Löffler, H., Ho, A. D., & Krämer, A. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0663 · Cited by 181 · see citing works
Limiting the Proliferation of Polyploid Cells
Ganem, N. J., & Pellman, D. S. (2007) · Cell · doi:10.1016/j.cell.2007.10.024 · Cited by 174 · see citing works
Hepatocyte polyploidization and its association with pathophysiological processes
Wang, M.-J., Chen, F., Lau, J. T. Y., & Hu, Y.-P. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.167 · Cited by 161 · see citing works
Understanding Cytokinesis Failure
Normand, G., & King, R. W. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-6199-0_3 · Cited by 171 · see citing works
Polyploidy in tissue homeostasis and regeneration
Øvrebø, J. I., & Edgar, B. A. (2018) · Development · doi:10.1242/dev.156034 · Cited by 171 · see citing works
Liver tetraploidization is controlled by a new process of incomplete cytokinesis
Margall-Ducos, G., Celton-Morizur, S., Couton, D., Brégerie, O., & Desdouets, C. (2007) · Journal of Cell Science · doi:10.1242/jcs.016907 · Cited by 170 · see citing works
Self-citationE2F8 is essential for polyploidization in mammalian cells
Pandit, S. K., Westendorp, B., Nantasanti, S., van Liere, E., Tooten, P. C. J., Cornelissen, P. W. A., Toussaint, M. J. M., Lamers, W. H., & de Bruin, A. (2012) · Nature Cell Biology · doi:10.1038/ncb2585 · Cited by 168 · see citing works
Physiological significance of polyploidization in mammalian cells.
Pandit, S. K., Westendorp, B., & de Bruin, A. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.06.002 · Cited by 165 · see citing works
To divide or not to divide: revisiting liver regeneration
Miyaoka, Y., & Miyajima, A. (2013) · Cell Division · doi:10.1186/1747-1028-8-8 · Cited by 156 · see citing works
Separase: a universal trigger for sister chromatid disjunction but not chromosome cycle progression
Wirth, K. G., Wutz, G., Kudo, N. R., Desdouets, C., Zetterberg, A., Taghybeeglu, S., Seznec, J., Margall-Ducos, G., Ricci, R., Firnberg, N., et al. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200506119 · Cited by 156 · see citing works
Self-citationRoh, H. C., Tsai, L. T.-Y., Lyubetskaya, A., Tenen, D. E., Kumari, M., & Rosen, E. D. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.087 · Cited by 150 · see citing works
Centrosome function in cancer: guilty or innocent?
Zyss, D., & Gergely, F. V. (2009) · Trends in Cell Biology · doi:10.1016/j.tcb.2009.04.001 · Cited by 149 · see citing works
Celton-Morizur, S., Merlen, G., Couton, D., Margall-Ducos, G., & Desdouets, C. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38677 · Cited by 145 · see citing works
Self-citationChromosome Segregation Fidelity in Epithelia Requires Tissue Architecture
Knouse, K. A., Lopez, K. E., Bachofner, M., & Amon, A. (2018) · Cell · doi:10.1016/j.cell.2018.07.042 · Cited by 134 · see citing works
Umbilical cord blood stem cells
Rogers, I. M., & Casper, R. F. (2004) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2004.06.004 · Cited by 136 · see citing works
The Polyploid State Restricts Hepatocyte Proliferation and Liver Regeneration in Mice
Wilkinson, P. D., Delgado, E. R., Alencastro, F., Leek, M. P., Roy, N., Weirich, M. P., Stahl, E. C., Otero, P. A., Chen, M. I., Brown, W. K., et al. (2019) · Hepatology · doi:10.1002/hep.30286 · Cited by 135 · see citing works
Centrosome clustering and chromosomal (in)stability: A matter of life and death
Krämer, A., Maier, B., & Bártek, J. (2011) · Molecular Oncology · doi:10.1016/j.molonc.2011.05.003 · Cited by 133 · see citing works
Formation of human hepatocytes by human hematopoietic stem cells in sheep
Almeida-Porada, G. D., Porada, C. D., Chamberlain, J., Torabi, A., & Zanjani, E. D. (2004) · Blood · doi:10.1182/blood-2004-01-0259 · Cited by 130 · see citing works
Cytokinesis, ploidy and aneuploidy
Lacroix, B., & Maddox, A. (2012) · Journal of Pathology · doi:10.1002/path.3013 · Cited by 144 · see citing works
Tao, Y., Ruan, J., Yeh, S., Lu, X., Wang, Y., Zhai, W., Cai, J., Ling, S., Gong, Q., Chong, Z., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108715108 · Cited by 129 · see citing works
Polyploidization of liver cells
Celton‐Morizur, S., & Desdouets, C. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-6199-0_8 · Cited by 122 · see citing works
Self-citationPloidy Variation in Fungi: Polyploidy, Aneuploidy, and Genome Evolution
Todd, R. T., Forche, A., & Selmecki, A. (2017) · Microbiology Spectrum · doi:10.1128/microbiolspec.funk-0051-2016 · Cited by 121 · see citing works
Single-Cell Analysis Uncovers Clonal Acinar Cell Heterogeneity in the Adult Pancreas
Wollny, D., Zhao, S., Everlien, I., Lun, X., Brunken, J., Brüne, D., Ziebell, F., Tabansky, I., Weichert, W., Marciniak-Czochra, A. K., et al. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.10.002 · Cited by 114 · see citing works
Vinciguerra, P., Godinho, S. A., Parmar, K., Pellman, D. S., & D’Andrea, A. D. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43391 · Cited by 115 · see citing works
Ploidy Reductions in Murine Fusion-Derived Hepatocytes
Duncan, A. W., Hickey, R., Paulk, N. K., Culberson, A. J., Olson, S. B., Finegold, M. J., & Grompe, M. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000385 · Cited by 113 · see citing works
Zanet, J., Freije, A., Ruiz‐Soto, M., Coulon, V., Sanz, J. R., Chiésa, J., & Gandarillas, A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015701 · Cited by 111 · see citing works
p38 MAPK: A dual role in hepatocyte proliferation through reactive oxygen species
Tormos, A. M., Taléns‐Visconti, R., Nebreda, Á. R., & Sastre, J. (2013) · Free Radical Research · doi:10.3109/10715762.2013.821200 · Cited by 110 · see citing works
Dollé, M. E. T., Busuttil, R. A., Garcia, A. M., Wijnhoven, S., van Drunen, E., Niedernhofer, L. J., van der Horst, G. T. J., Hoeijmakers, J. H. J., STEEG, H. V., & Vijg, J. (2006) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2005.11.008 · Cited by 109 · see citing works
Biotechnology Challenges to In Vitro Maturation of Hepatic Stem Cells
Chen, C., Soto–Gutiérrez, A., Baptista, P. M., & Spee, B. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.01.066 · Cited by 103 · see citing works
Changes to hepatocyte ploidy and binuclearity profiles during human chronic viral hepatitis
Toyoda, H., Bregerie, O., Vallet, A., Nalpas, B., Pivert, G., Brechot, C., & Desdouets, C. (2005) · Gut · doi:10.1136/gut.2004.043893 · Cited by 105 · see citing works
Self-citationReversal of Hepatocyte Senescence After Continuous In Vivo Cell Proliferation
Wang, M., Chen, F., Li, J., Liu, C.-C., Zhang, H., Xia, Y., Yu, B., You, P., Xiang, D., Lu, L., et al. (2014) · Hepatology · doi:10.1002/hep.27094 · Cited by 103 · see citing works
ESRP2 controls an adult splicing programme in hepatocytes to support postnatal liver maturation
Bhate, A., Parker, D. J., Bebee, T. W., Ahn, J., Arif, W., Rashan, E. H., Chorghade, S., Chau, A., Lee, J.-H., Anakk, S., et al. (2015) · Nature Communications · doi:10.1038/ncomms9768 · Cited by 103 · see citing works
Polyploidy spectrum: a new marker in HCC classification
Bou-Nader, M., Caruso, S., Donné, R., Celton-Morizur, S., Calderaro, J., Gentric, G., Cadoux, M., L’Hermitte, A., Klein, C., Guilbert, T., et al. (2019) · Gut · doi:10.1136/gutjnl-2018-318021 · Cited by 91 · see citing works
Self-citationLiver-Specific pRB Loss Results in Ectopic Cell Cycle Entry and Aberrant Ploidy
Mayhew, C. N., Bosco, E. E., Fox, S. R., Okaya, T., Tarapore, P., Schwemberger, S. J., Babcock, G. F., Lentsch, A. B., Fukasawa, K., & Knudsen, E. S. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4221 · Cited by 101 · see citing works
Morales-Navarrete, H., Segovia-Miranda, F., Klukowski, P., Meyer, K., Nonaka, H., Marsico, G., Chernykh, M., Kalaidzidis, A., Zerial, M., & Kalaidzidis, Y. (2015) · eLife · doi:10.7554/elife.11214 · Cited by 98 · see citing works
p53 REGULATES A MITOTIC TRANSCRIPTION PROGRAM AND DETERMINES PLOIDY IN NORMAL MOUSE LIVER
Kurinna, S., Stratton, S., Coban, Z., Schumacher, J. M., Grompe, M., Duncan, A. W., & Barton, M. (2013) · Hepatology · doi:10.1002/hep.26233 · Cited by 92 · see citing works
A critical role of integrin-linked kinase, ch-TOG and TACC3 in centrosome clustering in cancer cells
Fielding, A. B., Lim, S., Montgomery, K. D., Dobreva, I., & Dedhar, S. (2010) · Oncogene · doi:10.1038/onc.2010.431 · Cited by 90 · see citing works
Covo, S., Westmoreland, J. W., Gordenin, D. A., & Resnick, M. A. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001006 · Cited by 89 · see citing works
Nelsen, C. J., Kuriyama, R., Hirsch, B. A., Negron, V. C., Lingle, W. L., Goggin, M. M., Stanley, M. W., & Albrecht, J. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407105200 · Cited by 89 · see citing works
Never tear us apart – the importance of centrosome clustering
Marthiens, V., Piel, M., & Basto, R. (2012) · Journal of Cell Science · doi:10.1242/jcs.094797 · Cited by 89 · see citing works
Anastasia, L., Sampaolesi, M., Papini, N., Oleari, D., Lamorte, G., Tringali, C., Monti, E., Galli, D., Tettamanti, G., Cossu, G., et al. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401958 · Cited by 85 · see citing works
MicroRNA‐122 regulates polyploidization in the murine liver
Hsu, S., Delgado, E. R., Otero, P. A., Teng, K., Kutay, H., Meehan, K. M., Moroney, J. B., Monga, J. K., Hand, N. J., Friedman, J. R., et al. (2016) · Hepatology · doi:10.1002/hep.28573 · Cited by 84 · see citing works
Bilanges, B., Alliouachene, S., Pearce, W. P., Morelli, D., Szabadkai, G., Chung, Y.-L., Chicanne, G., Valet, C., Hill, J. M., Voshol, P. J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01969-4 · Cited by 82 · see citing works
S6 kinase 1 is required for rapamycin-sensitive liver proliferation after mouse hepatectomy
Espeillac, C., Mitchell, C., Celton‐Morizur, S., Chauvin, C., Koka, V., Gillet, C., Albrecht, J. H., Desdouets, C., & Pende, M. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44203 · Cited by 80 · see citing works
Self-citationGasnereau, I., Boissan, M., Margall-Ducos, G., Couchy, G., Wendum, D., Bourgain‐Guglielmetti, F., Desdouets, C., Lacombe, M., Zucman‐Rossi, J., & Sobczak‐Thépot, J. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2011.09.040 · Cited by 79 · see citing works
Self-citationFougère‐Deschatrette, C., Imaizumi‐Scherrer, T., Strick‐Marchand, H., Morosan, S., Charneau, P., Kremsdorf, D., Faust, D. M., & Weiss, M. C. (2006) · Stem Cells · doi:10.1634/stemcells.2006-0009 · Cited by 79 · see citing works
Inactivation of the Class II PI3K-C2β Potentiates Insulin Signaling and Sensitivity
Alliouachene, S., Bilanges, B., Chicanne, G., Anderson, K. E., Pearce, W. P., Ali, K., Valet, C., Posor, Y., Low, P. C., Chaussade, C., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.052 · Cited by 78 · see citing works
Centrosome aberrations in hematological malignancies
Krämer, A., Neben, K., & Ho, A. D. (2005) · Cell Biology International · doi:10.1016/j.cellbi.2005.03.004 · Cited by 78 · see citing works
Hepatocytes Polyploidization and Cell Cycle Control in Liver Physiopathology
Gentric, G., Desdouets, C., & Celton-Morizur, S. (2012) · International Journal of Hepatology · doi:10.1155/2012/282430 · Cited by 79 · see citing works
Self-citationWang, J., Batourina, E., Schneider, K., Souza, S. S., Swayne, T., Liu, C., George, C., Tate, T., Dan, H.-B., Wiessner, G., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.09.042 · Cited by 71 · see citing works
Diploid hepatocytes drive physiological liver renewal in adult humans
Heinke, P., Rost, F., Rode, J., Trus, P., Simonova, I., Lázár, E., Feddema, J., Welsch, T., Alkass, K., Salehpour, M., et al. (2022) · Cell Systems · doi:10.1016/j.cels.2022.05.001 · Cited by 73 · see citing works
Abnormal mitosis triggers p53-dependent cell cycle arrest in human tetraploid cells
Kuffer, C., Kuznetsova, A. Y., & Štorchová, Z. (2013) · Chromosoma · doi:10.1007/s00412-013-0414-0 · Cited by 73 · see citing works
Polyploidy and liver proliferation
Gentric, G., Celton-Morizur, S., & Desdouets, C. (2012) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2011.05.011 · Cited by 73 · see citing works
Self-citationPotapova, T., Seidel, C. W., Box, A., Rancati, G. I., & Li, R. (2016) · Molecular Biology of the Cell · doi:10.1091/mbc.e16-05-0268 · Cited by 67 · see citing works
Microarray analysis of gene expression of mouse hepatocytes of different ploidy
Lü, P., Prost, S., Caldwell, H., Tugwood, J. D., Betton, G. R., & Harrison, D. J. (2007) · Mammalian Genome · doi:10.1007/s00335-007-9048-y · Cited by 69 · see citing works
Cellular and molecular basis of liver regeneration
Bangru, S., & Kalsotra, A. (2020) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.12.004 · Cited by 66 · see citing works
The Cardiomyocyte Cell Cycle in Hypertrophy, Tissue Homeostasis, and Regeneration
Zebrowski, D. C., & Engel, F. B. (2013) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/112_2013_12 · Cited by 62 · see citing works
p27Kip1 controls cytokinesis via the regulation of citron kinase activation
Serres, M. P., Kossatz-Boehlert, U., Chi, Y., Roberts, J. M., Malek, N. P., & Besson, A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60376 · Cited by 62 · see citing works
Torre, C., Benhamouche, S., Mitchell, C., Godard, C., Veber, P., Letourneur, F., Cagnard, N., Jacques, S., Finzi, L., Perret, C., et al. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2010.10.021 · Cited by 60 · see citing works
Zerrad-Saadi, A., Lambert-Blot, M., Mitchell, C., Bretes, H., de l’Hortet, A. C., Baud, V., Chéreau, F., Sotiropoulos, A., Kopchick, J. J., Liao, L., et al. (2011) · Endocrinology · doi:10.1210/en.2010-1193 · Cited by 60 · see citing works
Self-citationJones, M. R., & Ravid, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m308406200 · Cited by 60 · see citing works
Papeleu, P., Vanhaecke, T., Elaut, G., Vinken, M., Henkens, T., Snykers, S., & Rogiers, V. (2005) · Critical Reviews in Toxicology · doi:10.1080/10408440590935639 · Cited by 60 · see citing works
Leone, M., & Engel, F. B. (2019) · Clinical Science · doi:10.1042/cs20180560 · Cited by 57 · see citing works
Morten, K., Ashley, N., Wijburg, F. A., Hadžić, N., Parr, J. R., Jayawant, S., Adams, S., Bindoff, L. A., Bakker, H. D., Mieli‐Vergani, G., et al. (2007) · Mitochondrion · doi:10.1016/j.mito.2007.09.001 · Cited by 58 · see citing works
The Space of Disse: The Liver Hub in Health and Disease
Sanz-García, C., Fernández-Iglesias, A., Gracia-Sancho, J., Arráez-Aybar, L. A., Nevzorova, Y. A., & Cubero, F. J. (2021) · Livers · doi:10.3390/livers1010002 · Cited by 57 · see citing works
Tanaka, H., Goto, H., Inoko, A., Makihara, H., Enomoto, A., Horimoto, K., Matsuyama, M., Kurita, K., Izawa, I., & Inagaki, M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.633891 · Cited by 55 · see citing works
Gene profiling of maternal hepatic adaptations to pregnancy
Bustamante, J. J., Copple, B. L., Soares, M. J., & Dai, G. (2009) · Liver International · doi:10.1111/j.1478-3231.2009.02183.x · Cited by 55 · see citing works
- 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 › Agricultural and Biological Sciences › Plant Science › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
