Polyploidy in tissue homeostasis and regeneration
Open accessAbstract
Polyploid cells, which contain multiple copies of the typically diploid genome, are widespread in plants and animals. Polyploidization can be developmentally programmed or stress induced, and arises from either cell-cell fusion or a process known as endoreplication, in which cells replicate their DNA but either fail to complete cytokinesis or to progress through M phase entirely. Polyploidization offers cells several potential fitness benefits, including the ability to increase cell size and biomass production without disrupting cell and tissue structure, and allowing improved cell longevity through higher tolerance to genomic stress and apoptotic signals. Accordingly, recent studies have uncovered crucial roles for polyploidization in compensatory cell growth during tissue regeneration in the heart, liver, epidermis and intestine. Here, we review current knowledge of the molecular pathways that generate polyploidy and discuss how polyploidization is used in tissue repair and regeneration.
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?
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 [5]
Cites
Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation
Jopling, C., Sleep, E., Raya, M., Martí, M., Raya, A., & Belmonte, J. C. I. (2010) · Nature · doi:10.1038/nature08899 · Cited by 1,333 · see citing works
Liver Cell Polyploidization: A Pivotal Role for Binuclear Hepatocytes
Guidotti, J.-E., Brégerie, O., Robert, A., Debey, P., Brechot, C., & Desdouets, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300982200 · Cited by 315 · see citing works
de Bruin, A., Maiti, B., Jakoi, L., Timmers, C., Buerki, R., & Leone, G. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308105200 · Cited by 221 · see citing works
The Polyploid State Plays a Tumor-Suppressive Role in the Liver
Zhang, S., Zhou, K., Luo, X., Li, L., Tu, H.-C., Sehgal, A., Nguyen, L. H., Zhang, Y., Gopal, P., Tarlow, B. D., et al. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.01.010 · Cited by 180 · cited 1× · see citing works
“, 2018), as reported in hepatocytes (Zhang et al., 2018).”
E2F8 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 · cited 26× · see citing works
“This control involves the E2F family of transcription factors, which in mammals includes the activator E2Fs (E2F1-E2F3), the repressor E2Fs (E2F4-E2F6), and two atypical repressor E2Fs (E2F7 and E2F8) (Chen et al., 2009; van den Heuvel and Dyson, 2008).”
BackgroundInfluentialCanonical and atypical E2Fs regulate the mammalian endocycle
Chen, H.-Z., Ouseph, M. M., Li, J., Pécot, T., Chokshi, V., Kent, L., Bae, S., Byrne, M., Duran, C., Comstock, G., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2595 · Cited by 161 · see citing works
A coordinated global control over cellular transcription
Zhurinsky, J., Leonhard, K., Watt, S., Marguerat, S., Bähler, J., & Nurse, P. (2010) · Current Biology · doi:10.1016/j.cub.2010.10.002 · Cited by 148 · see citing works
The transcriptional response to tumorigenic polarity loss in Drosophila
Bunker, B. D., Nellimoottil, T. T., Boileau, R. M., Classen, A. K., & Bilder, D. (2015) · eLife · doi:10.7554/elife.03189 · Cited by 114 · 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 · cited 1× · see citing works
“This ability has been proposed to support regeneration of the mammalian liver upon chemotoxic stress and aging (Gentric et al., 2012; Gupta, 2000), and wound healing in Drosophila (Losick, 2016; Losick et al.”
BackgroundQi, Q.-R., Zhao, X.-Y., Zuo, R.-J., Wang, T.-S., Gu, X.-W., Liu, J.-L., & Yang, Z.-M. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1033593 · Cited by 58 · cited 3× · see citing works
“In TGCs, however, endocycles are promoted by elevated E2F8 expression (Qi et al., 2015), which is induced by progesterone through the EGFR/ERK/STAT3 signaling pathway.”
Background
Flagged first, then by citations
Cited by
Sorted by citations
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
“Physiological polyploidization occurs in a developmentally programmed manner in hepatocytes, cardiomyocytes, and megakaryocytes (Ovrebo and Edgar, 2018).”
BackgroundPolyploidy 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
The “life code”: A theory that unifies the human life cycle and the origin of human tumors
Liu, J. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.09.005 · Cited by 119 · see citing works
A common signature of cellular senescence; does it exist?
Sikora, E., Bielak-Żmijewska, A., & Mosieniak, G. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101458 · Cited by 120 · see citing works
Derks, W. J. A., & Bergmann, O. (2020) · Circulation Research · doi:10.1161/circresaha.119.315408 · Cited by 188 · see citing works
Cardiomyocyte Polyploidy and Implications for Heart Regeneration
Gan, P., Patterson, M., & Sucov, H. M. (2019) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021119-034618 · Cited by 87 · see citing works
“Polyploidy is also seen in a variety of cell types in invertebrate animals and in plants (1).”
BackgroundSurviving Acute Organ Failure: Cell Polyploidization and Progenitor Proliferation
Lazzeri, E., Angelotti, M. L., Conte, C., Anders, H., & Romagnani, P. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.02.006 · Cited by 82 · see citing works
Polyploid giant cancer cells and cancer progression
Zhou, X., Zhou, M., Zheng, M., Tian, S., Yang, X., Ning, Y., Li, Y., & Zhang, S. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1017588 · Cited by 76 · see citing works
“Both endoreduplication and cell fusion can induce the formation of PGCCs (Figure 1) (Niu et al., 2016; Liu, 2018; Øvrebø and Edgar, 2018; Chen et al., 2019; Moein et al., 2020).”
BackgroundHuman–chimpanzee fused cells reveal cis-regulatory divergence underlying skeletal evolution
Gokhman, D., Agoglia, R. M., Kinnebrew, M., Gordon, W. E., Sun, D., Bajpai, V. K., Naqvi, S., Chen, C., Chan, A. W. S., Chen, C., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00804-3 · Cited by 87 · see citing works
The “polyploid effect” in the breeding of aromatic and medicinal species
Iannicelli, J., Guariniello, J., Tossi, V. E., Regalado, J. J., Ciaccio, L. D., van Baren, C. M., Pitta-Alvarez, S. I., & Escandón, A. S. (2019) · Scientia Horticulturae · doi:10.1016/j.scienta.2019.108854 · Cited by 87 · see citing works
Targeting tumor cell senescence and polyploidy as potential therapeutic strategies
Saleh, T., Carpenter, V. J., Bloukh, S., & Gewirtz, D. A. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.12.010 · Cited by 70 · see citing works
Cohen, E., Allen, S. R., Sawyer, J. K., & Fox, D. T. (2018) · eLife · doi:10.7554/elife.38327 · Cited by 83 · see citing works
Polyploidy as a Fundamental Phenomenon in Evolution, Development, Adaptation and Diseases
Anatskaya, O. V., & Vinogradov, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073542 · Cited by 61 · see citing works
Velleuer, E., Dietrich, R., Pomjanski, N., Araujo, I. K. S. A., de Araujo, B. E. S., Sroka, I. C., Biesterfeld, S., Böcking, A., & Schramm, M. (2020) · Cancer Cytopathology · doi:10.1002/cncy.22249 · Cited by 61 · see citing works
A Genome-wide Library of MADM Mice for Single-Cell Genetic Mosaic AnalysisPreprint
Contreras, X., Davaatseren, A., Amberg, N., Hansen, A. H., Sonntag, J., Andersen, L., Bernthaler, T., Heger, A., Johnson, R. L., Schwarz, L. A., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.05.136192 · Cited by 12 · see citing works
“14 Cell Reports 35, 109274, June 22, 2021 One possible limitation or confounder for the interpretation of MADM-based cell labeling and gene dosage is cellular polyploidy (Øvrebø and Edgar 2018).”
BackgroundSolving the polyploid mystery in health and disease
Gjelsvik, K. J., Besen-McNally, R., & Losick, V. P. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.10.005 · Cited by 59 · see citing works
Chiara, L. D., Conte, C., Semeraro, R., Díaz-Bulnes, P., Angelotti, M. L., Mazzinghi, B., Molli, A., Antonelli, G., Landini, S., Melica, M. E., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33110-5 · Cited by 79 · see citing works
Song, Y.-W., Zhao, Y., Deng, Z., Zhao, R.-Y., & Huang, Q. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.724781 · Cited by 57 · see citing works
“Such mechanisms support organ growth and tissue homeostasis (15).”
BackgroundCell Cycle Re-entry in the Nervous System: From Polyploidy to Neurodegeneration
Nandakumar, S., Rozich, E., & Buttitta, L. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.698661 · Cited by 62 · see citing works
Therapy-induced polyploidization and senescence: Coincidence or interconnection?
Sikora, E., Czarnecka‐Herok, J., Bojko, A., & Sunderland, P. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.11.015 · Cited by 63 · see citing works
Liu, P., Wang, L., & Yu, H. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1410637 · Cited by 56 · see citing works
“Polyploid cells are present in various human tissues, including trophoblast giant cells (TGC), blood megakaryocytes, hepatocytes, skeletal muscle cells, and cardiomyocytes (Øvrebø and Edgar, 2018).”
BackgroundLeone, M., & Engel, F. B. (2019) · Clinical Science · doi:10.1042/cs20180560 · Cited by 57 · see citing works
Cancer regeneration: Polyploid cells are the key drivers of tumor progression.
Moein, S., Adibi, R., Meirelles, L. D. S., Nardi, N., & Gheisari, Y. (2020) · Biochimica et biophysica acta. Reviews on cancer · doi:10.1016/j.bbcan.2020.188408 · Cited by 53 · see citing works
Polyploidization: A Biological Force That Enhances Stress Resistance
Li, X., Zhang, L.-Y., Wei, X.-C., Datta, T., Wei, F., & Xie, Z.-P. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25041957 · Cited by 52 · see citing works
“Moreover, polyploidization offers numerous potential adaptive benefits at the cellular level, such as increased cell size and biomass without compromising cellular and tissue structure and enhanced cellular longevity through improved tolerance to genomic stress and apoptotic signals [24].”
BackgroundGauthier, B. R., & Comaills, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147281 · Cited by 67 · see citing works
“However, it was described in the case of live th t senescence could be reversible and hectaploid hepatocytes may re-enter mitosis, giving rise to tetraploid and diploid cells, which is a dynamic process referred to as a ‘ploidy conveyor’, highlighting the mitosis plasticity of such cells [31,32].”
BackgroundEpithelial proliferation and cell cycle dysregulation in kidney injury and disease
Lee, K., Gusella, G. L., & He, C. (2021) · Kidney International · doi:10.1016/j.kint.2021.03.024 · Cited by 56 · see citing works
Tagal, V., & Roth, M. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-1693 · Cited by 45 · see citing works
“Polyploidy canbealso stress and injury induced to allow improved cell longevity in the incidences such as tissue injury, chemotoxic exposure or mitotic catastrophe (51).”
BackgroundCohesin depleted cells rebuild functional nuclear compartments after endomitosis
Cremer, M., Brandstetter, K., Maiser, A., Rao, S. S. P., Schmid, V. J., Guirao‐Ortiz, M., Mitra, N., Mamberti, S., Klein, K. N., Gilbert, D. M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19876-6 · Cited by 58 · see citing works
Quantitative chemometric phenotyping of three-dimensional liver organoids by Raman spectral imaging
LaLone, V., Aizenshtadt, A., Goertz, J. A., Skottvoll, F. S., Mota, M. B., You, J.-L., Zhao, X.-Y., Berg, H. E., Stokowiec, J., Yu, M., et al. (2023) · Cell Reports Methods · doi:10.1016/j.crmeth.2023.100440 · Cited by 40
“Hepatocyte polyploidy is hypothesized to be an adaptive mechanism for enhanced metabolism and protein synthesis as well as a mechanism to increase tolerance to the genomic stress and apoptotic signals.(25,26) Higher number of binuclear cells and more active protein synthesis in 3D PHH could explain”
BackgroundHuman Cell Polyploidization: the Good and the Evil.
Zhang, J., Qiao, Q., Xu, H., Zhou, R., & Liu, X.-Z. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.04.005 · Cited by 40 · see citing works
Grendler, J., Lowgren, S., Mills, M. T., & Losick, V. P. (2018) · Development · doi:10.1242/dev.173005 · Cited by 40 · see citing works
The origins and functions of hepatic polyploidy
Zhang, S., Lin, Y.-H., Tarlow, B., & Zhu, H. (2019) · Cell Cycle · doi:10.1080/15384101.2019.1618123 · Cited by 38 · see citing works
Polyploid cardiomyocytes: implications for heart regeneration
Kirillova, A., Han, L., Liu, H., & Kühn, B. (2021) · Development · doi:10.1242/dev.199401 · Cited by 41 · see citing works
Asymmetric clustering of centrosomes defines the early evolution of tetraploid cells
Baudoin, N., Nicholson, J. M., Soto, K., Martin, O., Chen, J., & Cimini, D. (2019) · bioRxiv · doi:10.7554/elife.54565 · Cited by 38 · see citing works
IL6 supports long-term expansion of hepatocytes in vitro
Guo, R., Jiang, M., Wang, G., Li, B., Jia, X., Ai, Y., Chen, S., Tang, P., Liu, A., Yuan, Q., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-35167-8 · Cited by 36 · see citing works
Polyploidy in Xenopus lowers metabolic rate by decreasing total cell surface area
Cadart, C., Bartz, J., Oaks, G., Liu, M., & Heald, R. (2023) · Current Biology · doi:10.1016/j.cub.2023.03.071 · Cited by 36 · see citing works
Communal living: the role of polyploidy and syncytia in tissue biology
Peterson, N. G., & Fox, D. T. (2021) · Chromosome Research · doi:10.1007/s10577-021-09664-3 · Cited by 47 · see citing works
“N. G. Peterson · D. T. Fox (*) Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA e-mail: don.fox@duke.edu D. T. Fox Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA 1 3 and Duronio 2013; Øvrebø and Edgar 2018).”
MethodInfluentialRotelli, M. D., Policastro, R. A., Bolling, A. M., Killion, A. W., Weinberg, A. J., Dixon, M. J., Zentner, G. E., Walczak, C., Lilly, M. A., & Calvi, B. R. (2019) · PLoS Genetics · doi:10.1371/journal.pgen.1008253 · Cited by 37 · see citing works
“Cells also can switch to endoreplication in response to conditional stresses and environmental inputs, for example during tissue regeneration and cancer (Fox and Duronio, 2013; Losick et al., 2013; Øvrebø and Edgar, 2018).”
BackgroundInfluentialAltamirano, S., Li, Z.-M., Fu, M., Ding, M., Fulton, S. R., Yoder, J., Tran, V., & Nielsen, K. (2021) · bioRxiv · doi:10.1128/mbio.02509-21 · Cited by 35 · see citing works
“ment, tissue homeostasis, and a stress response in many multicellular eukaryotes (2).”
Skeletal Muscle Nuclei in Mice are not Post-mitotic
Borowik, A., Davidyan, A., Peelor, F. F., Volovičeva, E., Doidge, S. M., Bubak, M. P., Mobley, C. B., McCarthy, J. J., Dupont‐Versteegden, E. E., & Miller, B. F. (2022) · Function · doi:10.1093/function/zqac059 · Cited by 41 · see citing works
Regulation of endogenous cardiomyocyte proliferation: The known unknowns
Secco, I., & Giacca, M. (2023) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2023.04.001 · Cited by 34 · see citing works
Anatskaya, O. V., Vinogradov, A., Vainshelbaum, N., Giuliani, A., & Erenpreisa, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228759 · Cited by 31 · see citing works
Chiara, L. D., Conte, C., Antonelli, G., & Lazzeri, E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222011093 · Cited by 36 · see citing works
“Endoreplication is an evolutionarily conserved alternative cell cycle program, during which cells replicate their genomes without cytokinesis, resulting in polyploid cells [79,80].”
BackgroundWang, C.-H., & Spradling, A. (2019) · bioRxiv · doi:10.7554/elife.54096 · Cited by 30 · see citing works
“If the number of cells differs from normal or changes during growth, the remaining cells will proliferate for a greater or lesser number of endocycles until the target tissue size is achieved (Deng et al., 2001; Edgar et al., 2014; Ovrebo and Edgar, 2018).”
BackgroundProliferation and Maturation: Janus and the Art of Cardiac Tissue Engineering
Singh, B. N., Yücel, D., Garay, B. I., Tolkacheva, E. G., Kyba, M., Perlingeiro, R. C. R., van Berlo, J. H., & Ogle, B. M. (2023) · Circulation Research · doi:10.1161/circresaha.122.321770 · Cited by 39 · see citing works
Loss of Endogenously Cycling Adult Cardiomyocytes Worsens Myocardial Function
Bradley, L., Young, A. P., Li, H.-B., Billcheck, H. O., & Wolf, M. J. (2020) · Circulation Research · doi:10.1161/circresaha.120.318277 · Cited by 28 · see citing works
Anatskaya, O. V., & Vinogradov, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179691 · Cited by 27 · see citing works
Coupled oscillators coordinate collective germline growth
Doherty, C. A., Diegmiller, R., Kapasiawala, M., Gavis, E. R., & Shvartsman, S. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.02.015 · Cited by 27 · see citing works
“Increased DNA content is wellcorrelated with increased cell size (Orr-Weaver, 2015; Øvrebø and Edgar, 2018).”
BackgroundWnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade
Jin, Y., Anbarchian, T., Wu, P., Sarkar, A., Fish, M., Peng, W. C., & Nusse, R. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2203849119 · Cited by 26 · see citing works
Origins of cancer: ain’t it just mature cells misbehaving?
Cho, C. J., Brown, J. W., & Mills, J. C. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00099-0 · Cited by 30 · see citing works
“On the contrary, multinucleation has, to our knowledge, not been reported in somatic stem cells (Donne, Saroul-Aïnama et al, 2020; Øvrebø and Edgar, 2018).”
BackgroundCell enlargement modulated by GATA4 and YAP instructs the senescence-associated secretory phenotype
Joung, J., Heo, Y., Kim, Y., Kim, J., Choi, H., Jeon, T., Jang, Y., Kim, E.-J., Lee, S. H., Suh, J. M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56929-0 · Cited by 24 · see citing works
Rujano, M., Briand, D., Ðelić, B., Marc, J., & Spéder, P. (2022) · Nature Communications · doi:10.1038/s41467-022-32685-3 · Cited by 24 · see citing works
Hepatocyte Polyploidy: Driver or Gatekeeper of Chronic Liver Diseases
Donné, R., Sangouard, F., Celton‐Morizur, S., & Desdouets, C. (2021) · Cancers · doi:10.3390/cancers13205151 · Cited by 28 · see citing works
“Entry into mitosis is inhibited by two key events: (a) proteolysis of the mitotic cyclin B1 and the inhibition of mitotic-CDKs; (b) tight regulation of S-CDK activity (low levels of activity in G phase and high levels in S phase), re-inducing genome replication [12,27].”
BackgroundWeng, A., Maciel-Herrerias, M., Watanabe, S., Welch, L., Flozak, A. S., Grant, R., Aillon, R., Dada, L., Han, S., Hinchcliff, M., et al. (2021) · bioRxiv · doi:10.1101/2021.08.10.455833 · Cited by 23
“chromosomes during mitosis for stem cell renewal (28).”
BackgroundMethodInfluentialChamber-specific transcriptional responses in atrial fibrillation
Lipovsky, C. E., Jiménez, J., Guo, Q., Li, G., Yin, T., Hicks, S. C., Bhatnagar, S., Takahashi, K., Zhang, D. M., Brumback, B. D., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.135319 · Cited by 20 · see citing works
Determinants of Cardiac Growth and Size.Preprint
Heallen, T. R., Kadow, Z. A., Wang, J., & Martin, J. F. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a037150 · Cited by 22 · see citing works
“Other benefits of polyploidy include increased resistance to somatic mutations and a greater ability to adapt to stress and injury without undergoing mitosis (Øvrebø and Edgar 2018).”
BackgroundBroughton, K., Khieu, T., Nguyen, N., Rosa, M., Mohsin, S., Quijada, P. J., Wang, B.-Y. J., Echeagaray, O., Kubli, D. A., Kim, T., et al. (2019) · Communications Biology · doi:10.1038/s42003-019-0453-z · Cited by 22 · see citing works
Senotherapies: A novel strategy for synergistic anti-tumor therapy
Qi, X., Li, J., & Cao, J. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.103365 · Cited by 25 · see citing works
Implications of Polyploidy and Ploidy Alterations in Hepatocytes in Liver Injuries and Cancers
Matsumoto, T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169409 · Cited by 21 · see citing works
“Trophoblast giant cells are the best-studied cell types that undergo endocycles in mammals [20].”
BackgroundPolyploidy in development and tumor models in Drosophila
Costa, C. A. M., Wang, X., Ellsworth, C. R., & Deng, W. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.09.011 · Cited by 26 · see citing works
Persistent DNA damage signaling and DNA polymerase theta promote broken chromosome segregation
Clay, D. E., Bretscher, H. S., Jezuit, E. A., Bush, K. B., & Fox, D. T. (2021) · The Journal of Cell Biology · doi:10.1083/jcb.202106116 · Cited by 24 · see citing works
“At the second larval instar stage (L2), papillar cells undergo two rounds of endocycling (Fox and Duronio, 2013; Øvrebø and Edgar, 2018), where they replicate their genome content without cell division (Fig.”
BackgroundContreras, E. G., Glavic, Á., Brand, A. H., & Sierralta, J. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.0452-20.2021 · Cited by 19 · see citing works
Cutie, S., Payumo, A. Y., Lunn, D., & Huang, G. N. (2019) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2020.04.013 · Cited by 22 · see citing works
Whole-Genome Doubling as a source of cancer: how, when, where, and why?
Sanz‐Gómez, N., González-Álvarez, M., Rivas, J. D. L., & de Cárcer, G. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1209136 · Cited by 23 · see citing works
“In certain tissues, polyploidization fulfills a biological function as part of the developmental program of the cell (Øvrebø and Edgar, 2018; Anatskaya and Vinogradov, 2022).”
BackgroundThe antagonistic relationship between apoptosis and polyploidy in development and cancer
Herriage, H. C., Huang, Y., & Calvi, B. R. (2023) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2023.05.009 · Cited by 23 · see citing works
Regulation of chromatin organization during animal regeneration
Jia, X., Lin, W., & Wang, W. (2023) · Cell Regeneration · doi:10.1186/s13619-023-00162-x · Cited by 17 · see citing works
“2020; Ovrebo and Edgar 2018).”
BackgroundPolyploid giant cancer cells: Underlying Mechanisms, Signaling Pathways, and Therapeutic Strategies.
Temaj, G., Saha, S., Chichiarelli, S., Telkoparan-Akillilar, P., Nuhii, N., Hadziselimovic, R., & Saso, L. (2025) · Critical reviews in oncology/hematology · doi:10.1016/j.critrevonc.2025.104802 · Cited by 16 · see citing works
The Cardiac Sarcomere and Cell Cycle
Pettinato, A. M., Ladha, F. A., & Hinson, J. T. (2022) · Current Cardiology Reports · doi:10.1007/s11886-022-01682-9 · Cited by 16 · see citing works
Endomitosis controls tissue-specific gene expression during development
van Rijnberk, L. M., Barrull-Mascaró, R., van der Palen, R. L., Schild, E. S., Korswagen, H., & Galli, M. (2021) · bioRxiv · doi:10.1371/journal.pbio.3001597 · Cited by 16 · see citing works
Glennon, E. K. K., Austin, L. S., Arang, N., Kain, H., Mast, F. D., Vijayan, K., Aitchison, J., Kappe, S., & Kaushansky, A. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.02.085 · Cited by 16
“Polyploidy is a common feature of hepatocytes in both mice and humans and is thought to play a role in liver regeneration (Øvrebø and Edgar, 2018).”
Pham, P.-L., Li, Y.-X., Guo, H., Zeng, R.-Z., Xie, L., Zhang, Z.-S., Chen, J.-J., Su, Q., & Xia, Q. (2019) · Hortscience · doi:10.21273/hortsci14310-19 · Cited by 15
Cell cycle variants during Drosophila male accessory gland development
Box, A., Ramesh, N. A., Nandakumar, S., Church, S. J., Prasad, D., Afrakhteh, A., Taichman, R., & Buttitta, L. A. (2024) · G3 · doi:10.1093/g3journal/jkae089 · Cited by 13
“Increased ploidy can contribute to increased biosynthesis, as is the case with Drosophila nurse cells (Orr-Weaver 2015; Inge Øvrebø and Edgar 2018), and recently, the secondary cells of the adult AG have been shown to endocycle in response to mating (Leiblich et al .”
BackgroundCHRONOCRISIS: When Cell Cycle Asynchrony Generates DNA Damage in Polyploid Cells
Gemble, S., & Basto, R. (2020) · Bioessays · doi:10.1002/bies.202000105 · Cited by 12 · see citing works
An RNAi Screen for Genes Required for Growth ofDrosophilaWing Tissue
Rotelli, M. D., Bolling, A. M., Killion, A. W., Weinberg, A. J., Dixon, M. J., & Calvi, B. R. (2019) · G3 Genes Genomes Genetics · doi:10.1534/g3.119.400581 · Cited by 15 · see citing works
Histone stress: an unexplored source of chromosomal instability in cancer?
Miles, D. M., Desdouets, C., & Géli, V. (2019) · Current Genetics · doi:10.1007/s00294-019-00967-x · Cited by 12
The Controversial Role of Polyploidy in Hepatocellular Carcinoma
Wang, N., Hao, F., Shi, Y., & Wang, J.-Q. (2021) · OncoTargets and Therapy · doi:10.2147/ott.s340435 · Cited by 11 · see citing works
“Generally, the formation of polyploid cells by diploid organisms mainly follows the three classic forms: cell fusion, endoreplication, and cytokinesis failure.(6,17,18) (Figure 1)”
BackgroundPopulation Dynamics and Neuronal Polyploidy in the Developing Neocortex
Jungas, T., Joseph, M., Fawal, M.-A., & Davy, A. (2020) · bioRxiv · doi:10.1093/texcom/tgaa063 · Cited by 11 · see citing works
Al-Naggar, I. M. A., Antony, M., Baker, D., Wang, L., Godoy, L. D. C., Kuo, C.-L., Fraser, M., Smith, P. P., Xu, M., & Kuchel, G. (2024) · Aging Cell · doi:10.1111/acel.14399 · Cited by 10 · see citing works
“In short, polyploidy confers stress resistance and increases the lifespan of cells by increasing their resistance to apoptosis, DNA damage and genetic instability, thus allowing their survival in conditions where diploid cells would be unable to survive (Bailey et al., 2021 ; Ovrebo & Edgar, 2018 ).”
Maya-Maldonado, K., Cardoso-Jaime, V., Hernández-Martínez, S., Recio-Tótoro, B., Bello-Garcia, D., Hernández-Hernández, F. D. L. C., & Lanz-Mendoza, H. (2022) · Developmental and Comparative Immunology · doi:10.1016/j.dci.2022.104424 · Cited by 10
Tran, B. D., Nguyen, Y. D. H., Pham, T. L. A., Komori, K., Nguyen, T. Q. C., Taninaka, M., & Kamei, K. (2022) · Scientific Reports · doi:10.1038/s41598-022-08299-6 · Cited by 10
Nguyen, A., Dzulko, M., Murr, J., Yun, Y., Schneider, G., & Krämer, O. (2021) · Cells · doi:10.3390/cells10102520 · Cited by 10 · see citing works
“DNA contents above 4N are found in cells that failed to segregate the replicated genomes in G2/M phase and underwent endomitosis [54].”
BackgroundHarmansa, S., & Lecuit, T. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.21.614249 · Cited by 3 · see citing works
“A commonly employed process that allows cells to increase their volume is to increase the cell's DNA content via endoreplication 31,33 .”
Molinuevo, R., Menendez, J., Cadle, K., Ariqat, N., Choy, M. K., Lagousis, C. R. M., Thomas, G., Strietzel, C., Bubolz, J. W., & Hinck, L. (2024) · Nature Communications · doi:10.1038/s41467-024-47668-9 · Cited by 10 · see citing works
“When considering the necessity of expansive growth during pregnancy, it is evident that multiple tissues (liver, endometrium, placenta, mammary gland) depend on a strict balance of proliferation, differentiation, endoreplication, and apoptosis 25 .”
Identification of multinucleated cells in human kidney cortex: A way for tissue repairing?
Fantone, S., Tossetta, G., Graciotti, L., Galosi, A. B., Skrami, E., Marzioni, D., & Morroni, M. (2021) · Journal of Anatomy · doi:10.1111/joa.13595 · Cited by 8 · see citing works
Velarde, S. B., Quevedo, A., Estella, C., & Baonza, A. (2021) · PLoS Biology · doi:10.1371/journal.pbio.3001367 · Cited by 9
de Carvalho, S. S., Rodovalho, C. D. M., Gaviraghi, A., Mota, M. B. S., Jablonka, W., dos Santos, C. R., Nunes, R. D., Sá-Guimarães, T. E., Oliveira, D. S., Melo, A. C. A., et al. (2021) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0008915 · Cited by 12 · see citing works
Yanku, Y., Bitman-Lotan, E., Zohar, Y., Kurant, E., Zilke, N., Eilers, M., & Orian, A. (2018) · Cells · doi:10.3390/cells7100151 · Cited by 9 · see citing works
Chen, P., Wang, L., Long, Y., Peng, Z., Jing, C., Wei, S., Jia, X., Zhang, M., Dong, Z., Ding, X., et al. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.07.029 · Cited by 6 · see citing works
“In mammals, polyploid cells are isolated from external barriers because the process of cytoplasmic division does not occur, and the larger cell size increases mechanical tension and resistance [5].”
Misare, K. R., Ampolini, E. A., Gonzalez, H. C., Sullivan, K. A., Li, X., Miller, C., Sosseh, B., Dunne, J. B., Voelkel-Johnson, C., Gordon, K., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-45225-w · Cited by 8 · see citing works
In Vivo Methods to Monitor Cardiomyocyte Proliferation
Young, A. P., Bradley, L., & Wolf, M. J. (2022) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd9030073 · Cited by 8 · see citing works
“Polyploidy occurs throughout the plant and animal kingdoms [36,37].”
BackgroundWhole-Genome Duplications in Evolution, Ontogeny, and Pathology: Complexity and Emergency Reserves
Anatskaya, O. V., & Vinogradov, A. (2021) · Molecular Biology · doi:10.1134/s0026893321050022 · Cited by 8 · see citing works
“Ample data are additionally accumulating to demonstrate that polyploidy facilitates adaptation to oxidative, inflammatory, hypoxic, and genotoxic stress [27, 120].”
BackgroundInfluentialAdibi, R., Moein, S., & Gheisari, Y. (2021) · Advanced Biomedical Research · doi:10.4103/abr.abr_348_21 · Cited by 8
“Cell polyploidy is not restricted to cancers, but an evolutionarily conserved mechanism to support tissue regeneration and combat against stressors.[5] Formation of PGCCs can be induced by either natural tensions such as hypoxia, acidic condition, and mechanical pressures or by chemotherapy and radiotherapy.”
BackgroundPolyploidy promotes transformation of epithelial cells into nonprofessional phagocytes
Huang, Y., Costa, C. A. M., Ruiz, N. V., Wang, X., Jevitt, A. M., Breneman, C. M., Han, C., & Deng, W.-M. (2025) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.2427293122 · Cited by 7
The expanding roles of myonuclei in adult skeletal muscle health and function
Borowik, A., Murach, K. A., & Miller, B. F. (2024) · Biochemical Society Transactions · doi:10.1042/bst20241637 · Cited by 7 · see citing works
Wang, Y.-Q., Lan, Q.-G., Li, F., Xiong, J.-C., Xie, H., Gong, S.-Q., Yao, M.-Y., Lv, L.-J., Qin, S.-Z., Xin, W., et al. (2024) · Journal of the American Society of Nephrology · doi:10.1681/asn.0000000577 · Cited by 7
Surviving the Storm: The Role of Poly‐ and Depolyploidization in Tissues and Tumors
Zhao, Y., He, S., Zhao, M., & Huang, Q. (2024) · Advanced Science · doi:10.1002/advs.202306318 · Cited by 7 · see citing works
Ploidy inference from single-cell data: application to human and mouse cell atlases
Takeuchi, F., & Kato, N. (2024) · Genetics · doi:10.1093/genetics/iyae061 · Cited by 6 · see citing works
Tnni3k Influences Cardiomyocyte S-Phase Activity and Proliferation
Purdy, A. L., Swift, S. K., Sucov, H., & Patterson, M. (2023) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2023.08.004 · Cited by 7
The diverging role of CDC14B: from mitotic exit in yeast to cell fate control in humans
Partscht, P., & Schiebel, E. (2023) · EMBO Journal · doi:10.15252/embj.2023114364 · Cited by 7 · see citing works
“…cells) — emerges from various origins and can have different developmental significance (Gjelsvik et al , 2019; Donne et al , 2020), and in certain cases, reducing CDK1-cyclin B1 activity might be sufficient to increase cellular ploidy (Diril et al , 2012; Edgar et al , 2014; Øvrebø & Edgar, 2018).”
Cancer cell repopulation after therapy: which is the mechanism?
Prakash, R., & Telleria, C. M. (2023) · Oncoscience · doi:10.18632/oncoscience.577 · Cited by 8 · see citing works
“The polyploid giant cells arise as a consequence of endoreplication leading to the formation of mononucleated giant cells first, followed by cytokinetic failure and cell-cell fusion, thus giving rise to daughter cells able to proliferate for a long-term and carrying new chromosome alterations that cause distant metast…”
Background
- Authors
- Øvrebø, J. I., & Edgar, B. A.
- Affiliations
- Huntsman Cancer Institute (US)
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2018-07-15
- Volume
- 145
- Issue
- 14
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC10682953
- OpenAlex
- W2884971698
- Cited by
- 171
- References
- 0
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 21 · 2023: 19 · 2022: 21 · 2021: 32 · 2020: 21 · 2019: 22 · 2018: 4
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Huntsman Cancer Foundation
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- polyploidy, polyploidization, endoreplication, cell fusion, tissue regeneration, tissue homeostasis, apoptosis, cardiac regeneration, liver regeneration, epidermal regeneration, intestinal regeneration
- MeSH terms
- Animals, Cell Division, DNA Replication, Humans, Organ Specificity, Polyploidy, Regeneration, Stress, Physiological
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
