The origins and functions of hepatic polyploidy

References

• Markov AV, Kaznacheev IS. Evolutionary consequences of polyploidy in prokaryotes and the origin of mitosis and meiosis. Biol Direct. 2016;11:28.
   PubMed Web of Science ®Google Scholar
• Weiss-Schneeweiss H, Emadzade K, Jang T-S, et al. Evolutionary consequences, constraints and potential of polyploidy in plants. Cytogenet Genome Res. 2013;140(2–4):137–150.
   PubMed Web of Science ®Google Scholar
• Jiao Y, Wickett NJ, Ayyampalayam S, et al. Ancestral polyploidy in seed plants and angiosperms. Nature. 2011;473(7345):97–100.
   PubMed Web of Science ®Google Scholar
• Rieseberg LH, Willis JH. Plant speciation. Science. 2007;317(5840):910–914.
   PubMed Web of Science ®Google Scholar
• Meyers LA, Levin DA. On the abundance of polyploids in flowering plants. Evolution. 2006;60(6):1198–1206.
   PubMed Web of Science ®Google Scholar
• Adams KL, Wendel JF. Polyploidy and genome evolution in plants. Curr Opin Plant Biol. 2005;8(2):135–141.
   PubMed Web of Science ®Google Scholar
• De Bodt S, Maere S, Van de Peer Y. Genome duplication and the origin of angiosperms. Trends Ecol Evol. 2005;20(11):591–597.
   PubMed Web of Science ®Google Scholar
• Otto SP, Whitton J. Polyploid incidence and evolution. Annu Rev Genet. 2000;34:401–437.
   PubMed Web of Science ®Google Scholar
• Van de Peer Y, Mizrachi E, Marchal K. The evolutionary significance of polyploidy. Nat Rev Genet. 2017;18(7):411–424.
   PubMed Web of Science ®Google Scholar
• Wertheim B, Beukeboom LW, van de Zande L. Polyploidy in animals: effects of gene expression on sex determination, evolution and ecology. Cytogenet Genome Res. 2013;140(2–4):256–269.
   PubMed Web of Science ®Google Scholar
• Leggatt RA, Iwama GK Occurrence of polyploidy in the fishes. Rev Fish Biol Fish. 2003;13(3):9.
   Web of Science ®Google Scholar
• Tymowska J, Kobel HR. Karyotype analysis of Xenopus muelleri (Peters) and Xenopus laevis (Daudin), Pipidae. Cytogenetics. 1972;11(4):270–278.
   PubMedGoogle Scholar
• Le Comber S, Smith C. Polyploidy in fishes: patterns and processes. Biological Journal of the Linnean Society. 2004;82(4):11.
   Web of Science ®Google Scholar
• Schmid M, Evans BJ, Bogart JP. Polyploidy in Amphibia. Cytogenet Genome Res. 2015;145(3–4):315–330.
   PubMed Web of Science ®Google Scholar
• Dehal P, Boore JL. Two rounds of whole genome duplication in the ancestral vertebrate. PLoS Biol. 2005;3(10):e314.
   PubMed Web of Science ®Google Scholar
• Winkelmann M, Pfitzer P, Schneider W. Significance of polyploidy in megakaryocytes and other cells in health and tumor disease. Klin Wochenschr. 1987;65(23):1115–1131.
   PubMedGoogle Scholar
• Liu Z, Yue S, Chen X, et al. Regulation of cardiomyocyte polyploidy and multinucleation by CyclinG1. Circ Res. 2010;106(9):1498–1506.
   PubMed Web of Science ®Google Scholar
• Ishikawa H, Bischoff R, Holtzer H. Mitosis and intermediate-sized filaments in developing skeletal muscle. J Cell Biol. 1968;38(3):538–555.
   PubMed Web of Science ®Google Scholar
• Frade JM. Somatic tetraploidy in vertebrate neurons: implications in physiology and pathology. Commun Integr Biol. 2010;3(2):201–203.
   PubMedGoogle Scholar
• Celton-Morizur S, Desdouets C. Polyploidization of liver cells. Adv Exp Med Biol. 2010;676:123–135.
   PubMed Web of Science ®Google Scholar
• Sroga JM, Ma X, Das SK. Developmental regulation of decidual cell polyploidy at the site of implantation. Front Biosci (Schol Ed). 2012;4:1475–1486.
   PubMedGoogle Scholar
• Mori M, Kitazume M, Ose R, et al. Death effector domain-containing protein (DEDD) is required for uterine decidualization during early pregnancy in mice. J Clin Invest. 2011;121(1):318–327.
   PubMed Web of Science ®Google Scholar
• Fei F, Zhang D, Yang Z, et al. The number of polyploid giant cancer cells and epithelial-mesenchymal transition-related proteins are associated with invasion and metastasis in human breast cancer. J Exp Clin Cancer Res. 2015;34:158.
   PubMed Web of Science ®Google Scholar
• Mosieniak G, Sliwinska MA, Alster O, et al. Polyploidy formation in doxorubicin-treated cancer cells can favor escape from senescence. Neoplasia. 2015;17(12):882–893.
   PubMed Web of Science ®Google Scholar
• Nguyen HG, Ravid K. Polyploidy: mechanisms and cancer promotion in hematopoietic and other cells. Adv Exp Med Biol. 2010;676:105–122.
   PubMed Web of Science ®Google Scholar
• Storchova Z, Pellman D. From polyploidy to aneuploidy, genome instability and cancer. Nat Rev Mol Cell Biol. 2004;5(1):45–54.
   PubMed Web of Science ®Google Scholar
• Ovrebo JI, Edgar BA. Polyploidy in tissue homeostasis and regeneration. Development. 2018;145(14):1–16.
   PubMed Web of Science ®Google Scholar
• Gentric G, Desdouets C. Polyploidization in liver tissue. Am J Pathol. 2014;184(2):322–331.
   PubMed Web of Science ®Google Scholar
• Yaffe D, Feldman M. The formation of hybrid multinucleated muscle fibers from myoblasts of different genetic origin. Dev Biol. 1965;11:300–317.
   PubMed Web of Science ®Google Scholar
• Faggioli F, Sacco MG, Susani L, et al. Cell fusion is a physiological process in mouse liver. Hepatology. 2008;48(5):1655–1664.
   PubMed Web of Science ®Google Scholar
• Hammond MP, Laird CD. Control of DNA replication and spatial distribution of defined DNA sequences in salivary gland cells of Drosophila melanogaster. Chromosoma. 1985;91(3–4):279–286.
   PubMed Web of Science ®Google Scholar
• Royzman I, Hayashi-Hagihara A, Dej KJ, et al. The E2F cell cycle regulator is required for Drosophila nurse cell DNA replication and apoptosis. Mech Dev. 2002;119(2):225–237.
   PubMed Web of Science ®Google Scholar
• Ullah Z, Kohn MJ, Yagi R, et al. Differentiation of trophoblast stem cells into giant cells is triggered by p57/Kip2 inhibition of CDK1 activity. Genes Dev. 2008;22(21):3024–3036.
   PubMed Web of Science ®Google Scholar
• Gonçalves CR, Antonini S, Vianna-Morgante AM, et al. Developmental changes in the ploidy of mouse implanting trophoblast cells in vitro. Histochem Cell Biol. 2003;119(3):189–198.
   PubMed Web of Science ®Google Scholar
• Davoli T, Denchi EL, de Lange T. Persistent telomere damage induces bypass of mitosis and tetraploidy. Cell. 2010;141(1):81–93.
   PubMed Web of Science ®Google Scholar
• Mansilla S, Priebe W, Portugal J. Mitotic catastrophe results in cell death by caspase-dependent and caspase-independent mechanisms. Cell Cycle. 2006;5(1):53–60.
   PubMed Web of Science ®Google Scholar
• Rieder CL, Maiato H. Stuck in division or passing through: what happens when cells cannot satisfy the spindle assembly checkpoint. Dev Cell. 2004;7(5):637–651.
   PubMed Web of Science ®Google Scholar
• Brito DA, Rieder CL. Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint. Curr Biol. 2006;16(12):1194–1200.
   PubMed Web of Science ®Google Scholar
• Russell P, Hennessy BT, Li J, et al. Cyclin G1 regulates the outcome of taxane-induced mitotic checkpoint arrest. Oncogene. 2012;31(19):2450–2460.
   PubMed Web of Science ®Google Scholar
• Tsuda Y, Iimori M, Nakashima Y, et al. Mitotic slippage and the subsequent cell fates after inhibition of Aurora B during tubulin-binding agent-induced mitotic arrest. Sci Rep. 2017;7(1):16762.
   PubMedGoogle Scholar
• Dalton WB, Yang VW. Role of prolonged mitotic checkpoint activation in the formation and treatment of cancer. Future Oncol. 2009;5(9):1363–1370.
   PubMed Web of Science ®Google Scholar
• Ohashi A. Different cell fates after mitotic slippage: from aneuploidy to polyploidy. Mol Cell Oncol. 2016;3(2):e1088503.
   PubMed Web of Science ®Google Scholar
• Rengstl B, Newrzela S, Heinrich T, et al. Incomplete cytokinesis and re-fusion of small mononucleated Hodgkin cells lead to giant multinucleated Reed-Sternberg cells. Proc Natl Acad Sci U S A. 2013;110(51):20729–20734.
   PubMed Web of Science ®Google Scholar
• Lordier L, Jalil A, Aurade F, et al. Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling. Blood. 2008;112(8):3164–3174.
   PubMed Web of Science ®Google Scholar
• Trakala M, Rodríguez-Acebes S, Maroto M, et al. Functional reprogramming of polyploidization in megakaryocytes. Dev Cell. 2015;32(2):155–167.
   PubMed Web of Science ®Google Scholar
• Cao J, Wang J, Jackman CP, et al. Tension creates an endoreplication wavefront that leads regeneration of epicardial tissue. Dev Cell. 2017;42(6):600–615. e4.
   PubMed Web of Science ®Google Scholar
• Spiro Z, Heisenberg CP. Regeneration tensed up: polyploidy takes the lead. Dev Cell. 2017;42(6):559–560.
   PubMed Web of Science ®Google Scholar
• Lima JP. [Anatomy and physiology of the liver secretory apparatus]. Arq Gastroenterol. 1980;17(3):149–160.
   PubMedGoogle Scholar
• Michalopoulos GK. Principles of liver regeneration and growth homeostasis. Compr Physiol. 2013;3(1):485–513.
   PubMed Web of Science ®Google Scholar
• Margall-Ducos G, Celton-Morizur S, Couton D, et al. Liver tetraploidization is controlled by a new process of incomplete cytokinesis. J Cell Sci. 2007;120(Pt 20):3633–3639.
   PubMed Web of Science ®Google Scholar
• Guidotti J-E, Brégerie O, Robert A, et al. Liver cell polyploidization: a pivotal role for binuclear hepatocytes. J Biol Chem. 2003;278(21):19095–19101.
   PubMed Web of Science ®Google Scholar
• Duncan AW. Aneuploidy, polyploidy and ploidy reversal in the liver. Semin Cell Dev Biol. 2013;24(4):347–356.
   PubMed Web of Science ®Google Scholar
• Duncan AW, Hanlon Newell AE, Smith L, et al. Frequent aneuploidy among normal human hepatocytes. Gastroenterology. 2012;142(1):25–28.
   PubMed Web of Science ®Google Scholar
• Celton-Morizur S, Merlen G, Couton D, et al. The insulin/Akt pathway controls a specific cell division program that leads to generation of binucleated tetraploid liver cells in rodents. J Clin Invest. 2009;119(7):1880–1887.
   PubMed Web of Science ®Google Scholar
• Celton-Morizur S, Merlen G, Couton D, et al. Polyploidy and liver proliferation: central role of insulin signaling. Cell Cycle. 2010;9(3):460–466.
   PubMed Web of Science ®Google Scholar
• Miyaoka Y, Ebato K, Kato H, et al. Hypertrophy and unconventional cell division of hepatocytes underlie liver regeneration. Curr Biol. 2012;22(13):1166–1175.
   PubMed Web of Science ®Google Scholar
• Faktor VM, Uryvaeva IV. Progressive polyploidy in mouse liver following repeated hepatectomy. Tsitologiia. 1975;17(8):909–916.
   PubMedGoogle Scholar
• Yamada T, Sogawa K, Kim JK, et al. Increased polyploidy, delayed mitosis and reduced protein phosphatase-1 activity associated with excess copper in the Long Evans Cinnamon rat. Res Commun Mol Pathol Pharmacol. 1998;99(3):283–304.
   PubMedGoogle Scholar
• Gentric G, Maillet V, Paradis V, et al. Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease. J Clin Invest. 2015;125(3):981–992.
   PubMed Web of Science ®Google Scholar
• Wang B, Zhao L, Fish M, et al. Self-renewing diploid Axin2(+) cells fuel homeostatic renewal of the liver. Nature. 2015;524(7564):180–185.
   PubMed Web of Science ®Google Scholar
• Kietzmann T. Metabolic zonation of the liver: the oxygen gradient revisited. Redox Biol. 2017;11:622–630.
   PubMed Web of Science ®Google Scholar
• Benhamouche S, Decaens T, Godard C, et al. Apc tumor suppressor gene is the “zonation-keeper” of mouse liver. Dev Cell. 2006;10(6):759–770.
   PubMed Web of Science ®Google Scholar
• Tanami S, Ben-Moshe S, Elkayam A, et al. Dynamic zonation of liver polyploidy. Cell Tissue Res. 2017;368(2):405–410.
   PubMed Web of Science ®Google Scholar
• Cross JC. Genetic insights into trophoblast differentiation and placental morphogenesis. Semin Cell Dev Biol. 2000;11(2):105–113.
   PubMed Web of Science ®Google Scholar
• Huch M, Dorrell C, Boj SF, et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature. 2013;494(7436):247–250.
   PubMed Web of Science ®Google Scholar
• Raven A, Lu W-Y, Man TY, et al. Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration. Nature. 2017;547(7663):350–354.
   PubMed Web of Science ®Google Scholar
• Tarlow BD, Finegold MJ, Grompe M. Clonal tracing of Sox9+ liver progenitors in mouse oval cell injury. Hepatology. 2014;60(1):278–289.
   PubMed Web of Science ®Google Scholar
• Schaub JR, Malato Y, Gormond C, et al. Evidence against a stem cell origin of new hepatocytes in a common mouse model of chronic liver injury. Cell Rep. 2014;8(4):933–939.
   PubMed Web of Science ®Google Scholar
• Font-Burgada J, Shalapour S, Ramaswamy S, et al. Hybrid periportal hepatocytes regenerate the injured liver without giving rise to cancer. Cell. 2015;162(4):766–779.
   PubMed Web of Science ®Google Scholar
• Pu W, Zhang H, Huang X, et al. Mfsd2a+ hepatocytes repopulate the liver during injury and regeneration. Nat Commun. 2016;7:13369.
   PubMed Web of Science ®Google Scholar
• Lin, S., Nascimento EM, Gajera CR, et al. Distributed hepatocytes expressing telomerase repopulate the liver in homeostasis and injury. Nature. 2018;556(7700):244–248.
   Google Scholar
• Furuyama K, Kawaguchi Y, Akiyama H, et al. Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine. Nat Genet. 2011;43(1):34–41.
   PubMed Web of Science ®Google Scholar
• Carpentier R, Suñer RE, van Hul N, et al. Embryonic ductal plate cells give rise to cholangiocytes, periportal hepatocytes, and adult liver progenitor cells. Gastroenterology. 2011;141(4):1432–8, 1438 e1-4.
   PubMed Web of Science ®Google Scholar
• Zhang S, Zhou K, Luo X, et al. The polyploid state plays a tumor-suppressive role in the liver. Dev Cell. 2018;44(4):447–459. e5.
   PubMed Web of Science ®Google Scholar
• Pandit SK, Westendorp B, Nantasanti S, et al. E2F8 is essential for polyploidization in mammalian cells. Nat Cell Biol. 2012;14(11):1181–1191.
   PubMed Web of Science ®Google Scholar
• Conner EA, Lemmer ER, Sánchez A, et al. E2F1 blocks and c-Myc accelerates hepatic ploidy in transgenic mouse models. Biochem Biophys Res Commun. 2003;302(1):114–120.
   PubMed Web of Science ®Google Scholar
• Chen HZ, Ouseph MM, Li J, et al. Canonical and atypical E2Fs regulate the mammalian endocycle. Nat Cell Biol. 2012;14(11):1192–1202.
   PubMed Web of Science ®Google Scholar
• Nevzorova YA, Tschaharganeh D, Gassler N, et al. Aberrant cell cycle progression and endoreplication in regenerating livers of mice that lack a single E-type cyclin. Gastroenterology. 2009;137(2):691–703, 703 e1-6.
   PubMed Web of Science ®Google Scholar
• Kurinna S, Stratton SA, Coban Z, et al. p53 regulates a mitotic transcription program and determines ploidy in normal mouse liver. Hepatology. 2013;57(5):2004–2013.
   PubMed Web of Science ®Google Scholar
• Sheahan S, Bellamy COC, Treanor L, et al. Additive effect of p53, p21 and Rb deletion in triple knockout primary hepatocytes. Oncogene. 2004;23(8):1489–1497.
   PubMed Web of Science ®Google Scholar
• Mayhew CN, Bosco EE, Fox SR, et al. Liver-specific pRB loss results in ectopic cell cycle entry and aberrant ploidy. Cancer Res. 2005;65(11):4568–4577.
   PubMed Web of Science ®Google Scholar
• Diril MK, Ratnacaram CK, Padmakumar VC, et al. Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and suppression of DNA re-replication but not for liver regeneration. Proc Natl Acad Sci U S A. 2012;109(10):3826–3831.
   PubMed Web of Science ®Google Scholar
• Minamishima YA, Nakayama K, Nakayama K. Recovery of liver mass without proliferation of hepatocytes after partial hepatectomy in Skp2-deficient mice. Cancer Res. 2002;62(4):995–999.
   PubMed Web of Science ®Google Scholar
• Kim S-H, Jeon Y, Kim H-S, et al. Hepatocyte homeostasis for chromosome ploidization and liver function is regulated by Ssu72 protein phosphatase. Hepatology. 2016;63(1):247–259.
   PubMed Web of Science ®Google Scholar
• Li D, Cen J, Chen X, et al. Hepatic loss of survivin impairs postnatal liver development and promotes expansion of hepatic progenitor cells in mice. Hepatology. 2013;58(6):2109–2121.
   PubMed Web of Science ®Google Scholar
• Hsu SH, Delgado ER, Otero PA, et al. MicroRNA-122 regulates polyploidization in the murine liver. Hepatology. 2016;64(2):599–615.
   PubMed Web of Science ®Google Scholar
• Davoli T, de Lange T. The causes and consequences of polyploidy in normal development and cancer. Annu Rev Cell Dev Biol. 2011;27:585–610.
   PubMed Web of Science ®Google Scholar
• Lee HO, Davidson JM, Duronio RJ. Endoreplication: polyploidy with purpose. Genes Dev. 2009;23(21):2461–2477.
   PubMed Web of Science ®Google Scholar
• Miettinen TP, Pessa HKJ, Caldez MJ, et al. Identification of transcriptional and metabolic programs related to mammalian cell size. Curr Biol. 2014;24(6):598–608.
   PubMed Web of Science ®Google Scholar
• Salazar-Roa M, Malumbres M. Fueling the cell division cycle. Trends Cell Biol. 2017;27(1):69–81.
   PubMed Web of Science ®Google Scholar
• Ewald JC, Kuehne A, Zamboni N, et al. The yeast cyclin-dependent kinase routes carbon fluxes to fuel cell cycle progression. Mol Cell. 2016;62(4):532–545.
   PubMed Web of Science ®Google Scholar
• Lu P, Prost S, Caldwell H, et al. Microarray analysis of gene expression of mouse hepatocytes of different ploidy. Mamm Genome. 2007;18(9):617–626.
   PubMed Web of Science ®Google Scholar
• Yoo MJ, Liu X, Pires JC, et al. Nonadditive gene expression in polyploids. Annu Rev Genet. 2014;48:485–517.
   PubMed Web of Science ®Google Scholar
• Corbel C, Diabangouaya P, Gendrel A-V, et al. Unusual chromatin status and organization of the inactive X chromosome in murine trophoblast giant cells. Development. 2013;140(4):861–872.
   PubMed Web of Science ®Google Scholar
• Schoenfelder KP, Fox DT. The expanding implications of polyploidy. J Cell Biol. 2015;209(4):485–491.
   PubMed Web of Science ®Google Scholar
• Bahar Halpern K, Tanami S, Landen S, et al. Bursty gene expression in the intact mammalian liver. Mol Cell. 2015;58(1):147–156.
   PubMed Web of Science ®Google Scholar
• Zack TI, Schumacher SE, Carter SL, et al. Pan-cancer patterns of somatic copy number alteration. Nat Genet. 2013;45(10):1134–1140.
   PubMed Web of Science ®Google Scholar
• Kaneko Y, Knudson AG. Mechanism and relevance of ploidy in neuroblastoma. Genes Chromosomes Cancer. 2000;29(2):89–95.
   PubMed Web of Science ®Google Scholar
• Gusnanto A, Wood HM, Pawitan Y, et al. Correcting for cancer genome size and tumour cell content enables better estimation of copy number alterations from next-generation sequence data. Bioinformatics. 2012;28(1):40–47.
   PubMed Web of Science ®Google Scholar
• Carter SL, Cibulskis K, Helman E, et al. Absolute quantification of somatic DNA alterations in human cancer. Nat Biotechnol. 2012;30(5):413–421.
   PubMed Web of Science ®Google Scholar
• Shackney SE, Smith CA, Miller BW, et al. Model for the genetic evolution of human solid tumors. Cancer Res. 1989;49(12):3344–3354.
   PubMed Web of Science ®Google Scholar
• Fujiwara T, Bandi M, Nitta M, et al. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature. 2005;437(7061):1043–1047.
   PubMed Web of Science ®Google Scholar
• Davoli T, de Lange T. Telomere-driven tetraploidization occurs in human cells undergoing crisis and promotes transformation of mouse cells. Cancer Cell. 2012;21(6):765–776.
   PubMed Web of Science ®Google Scholar
• Reid BJ, Barrett MT, Galipeau PC, et al. Barrett’s esophagus: ordering the events that lead to cancer. Eur J Cancer Prev. 1996;5(Suppl 2):57–65.
   PubMedGoogle Scholar
• Levine DS, Sanchez CA, Rabinovitch PS, et al. Formation of the tetraploid intermediate is associated with the development of cells with more than four centrioles in the elastase-simian virus 40 tumor antigen transgenic mouse model of pancreatic cancer. Proc Natl Acad Sci U S A. 1991;88(15):6427–6431.
   PubMed Web of Science ®Google Scholar
• Margolis RL, Lohez OD, Andreassen PR. G1 tetraploidy checkpoint and the suppression of tumorigenesis. J Cell Biochem. 2003;88(4):673–683.
   PubMed Web of Science ®Google Scholar
• Andreassen PR, Lohez OD, Lacroix FB, et al. Tetraploid state induces p53-dependent arrest of nontransformed mammalian cells in G1. Mol Biol Cell. 2001;12(5):1315–1328.
   PubMed Web of Science ®Google Scholar
• Kuffer C, Kuznetsova AY, Storchova Z. Abnormal mitosis triggers p53-dependent cell cycle arrest in human tetraploid cells. Chromosoma. 2013;122(4):305–318.
   PubMed Web of Science ®Google Scholar
• Ganem NJ, Cornils H, Chiu S-Y, et al. Cytokinesis failure triggers hippo tumor suppressor pathway activation. Cell. 2014;158(4):833–848.
   PubMed Web of Science ®Google Scholar
• Knouse KA, Lopez KE, Bachofner M, et al. Chromosome segregation fidelity in epithelia requires tissue architecture. Cell. 2018;175(1):200–211. e13.
   PubMed Web of Science ®Google Scholar
• Wilkinson P.D., Delgado ER, Alencastro F, et al. The polyploid state restricts hepatocyte proliferation and liver regeneration. Hepatology. 2019;69(3):1242–1258.
   Web of Science ®Google Scholar
• Zhang S, Li L, Kendrick SL, et al. TALEN-mediated somatic mutagenesis in murine models of cancer. Cancer Res. 2014;74(18):5311–5321.
   PubMed Web of Science ®Google Scholar
• Lucchetta EM, Ohlstein B. Amitosis of polyploid cells regenerates functional stem cells in the drosophila intestine. Cell Stem Cell. 2017;20(5):609–620. e6.
   PubMed Web of Science ®Google Scholar
• Duncan AW, Taylor MH, Hickey RD, et al. The ploidy conveyor of mature hepatocytes as a source of genetic variation. Nature. 2010;467(7316):707–710.
   PubMed Web of Science ®Google Scholar
• Wang MJ, Chen F, Li J-X, et al. Reversal of hepatocyte senescence after continuous in vivo cell proliferation. Hepatology. 2014;60(1):349–361.
   PubMed Web of Science ®Google Scholar
• Knouse KA, Wu J, Whittaker CA, et al. Single cell sequencing reveals low levels of aneuploidy across mammalian tissues. Proc Natl Acad Sci U S A. 2014;111(37):13409–13414.
   PubMed Web of Science ®Google Scholar
• Duncan AW, Soto-Gutierrez A. Liver repopulation and regeneration: new approaches to old questions. Curr Opin Organ Transplant. 2013;18(2):197–202.
   PubMed Web of Science ®Google Scholar
• Bouchonville K, Forche A, Tang KES, et al. Aneuploid chromosomes are highly unstable during DNA transformation of Candida albicans. Eukaryot Cell. 2009;8(10):1554–1566.
   PubMedGoogle Scholar
• Selmecki AM, Maruvka YE, Richmond PA, et al. Polyploidy can drive rapid adaptation in yeast. Nature. 2015;519(7543):349–352.
   PubMed Web of Science ®Google Scholar
• Chao D-Y, Dilkes B, Luo H, et al. Polyploids exhibit higher potassium uptake and salinity tolerance in Arabidopsis. Science. 2013;341(6146):658–659.
   PubMed Web of Science ®Google Scholar
• Duncan AW, Hanlon Newell AE, Bi W, et al. Aneuploidy as a mechanism for stress-induced liver adaptation. J Clin Invest. 2012;122(9):3307–3315.
   PubMed Web of Science ®Google Scholar
• González-Rosa JM, Sharpe M, Field D, et al. Myocardial polyploidization creates a barrier to heart regeneration in zebrafish. Dev Cell. 2018;44(4):433–446. e7.
   PubMed Web of Science ®Google Scholar