Cell competition describes the process in which cells of greater fitness are capable of sensing and instructing elimination of lesser fit mutant cells. Since its discovery in Drosophila, cell competition has been established as a critical regulator of organismal development, homeostasis, and disease progression. It is therefore unsurprising that stem cells (SCs), which are central to these processes, harness cell competition to remove aberrant cells and preserve tissue integrity. Here, we describe pioneering studies of cell competition across a variety of cellular contexts and organisms, with the ultimate goal of better understanding competition in mammalian SCs. Furthermore, we explore the modes through which SC competition takes place and how this facilitates normal cellular function or contributes to pathological states. Finally, we discuss how understanding of this critical phenomenon will enable targeting of SC-driven processes, including regeneration and tumor progression.
This is a preview of subscription content, access via your institution
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Fuchs Y, Steller H. Live to die another way: modes of programmed cell death and the signals emanating from dying cells. Nat Rev Mol Cell Biol. 2015;16:329–44.
Soteriou D, Fuchs Y. A matter of life and death: stem cell survival in tissue regeneration and tumour formation. Nat Rev Cancer. 2018;18:187–201.
Koren E, Fuchs Y. Modes of regulated cell death in cancer. Cancer Discov. 2021;11:245–65.
Morata G. Cell competition: a historical perspective. Dev Biol. 2021;476:33–40.
Levayer R, Moreno E. Mechanisms of cell competition: themes and variations. J Cell Biol. 2013;200:689–98.
Cosentino K, García-Sáez AJ. Bax and Bak pores: are we closing the circle? Trends Cell Biol. 2017;27:266–75.
Walczak H. Death receptor-ligand systems in cancer, cell death, and inflammation. Cold Spring Harb Perspect Biol. 2013;5:a008698.
Morata G, Ripoll P. Minutes: mutants of drosophila autonomously affecting cell division rate. Dev Biol. 1975;42:211–21.
Simpson P, Morata G. Differential mitotic rates and patterns of growth in compartments in the Drosophila wing. Dev Biol. 1981;85:299–308.
Cohen B, Simcox AA, Cohen SM. Allocation of the thoracic imaginal primordia in the Drosophila embryo. Development. 1993;117:597–608.
Marygold SJ, Roote J, Reuter G, Lambertsson A, Ashburner M, Millburn GH, et al. The ribosomal protein genes and Minute loci of Drosophila melanogaster. Genome Biol. 2007;8:R216.
Lindsley DL, Grell EH. Genetic variations of Drosophila melanogaster. Science 1968;162:993–993.
Moreno E, Basler K, Morata G. Cells compete for Decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature. 2002;416:755–9.
Moreno E, Basler K. DMyc transforms cells into super-competitors. Cell. 2004;117:117–29.
de la Cova C, Abril M, Bellosta P, Gallant P, Johnston LA. Drosophila Myc regulates organ size by inducing cell competition. Cell 2004;117:107–16.
Tolwinski NS. Introduction: Drosophila-a model system for developmental biology. J Dev Biol. 2017;5:9.
Baker NE. Emerging mechanisms of cell competition. Nat Rev Genet. 2020;21:683–97.
Hanna JH, Saha K, Jaenisch R. Pluripotency and cellular reprogramming: facts, hypotheses, unresolved issues. Cell. 2010;143:508–25.
Evans M, Kaufman M. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292:154–6.
Sionov RV, Haupt Y. The cellular response to p53: the decision between life and death. Oncogene. 1999;18:6145–57.
Vousden KH, Lu X. Live or let die: the cell’s response to p53. Nat Rev Cancer. 2002;2:594–604.
Tarkowski AK, Witkowska A, Opas J. Development of cytochalasin B-induced tetraploid and diploid/tetraploid mosaic mouse embryos. J Embryol Exp Morphol. 1977;41:47–64.
Nagy A, Gocza E, Merentes Diaz E, Prideaux VR, Ivanyi E, Markkl M, et al. Embryonic stem cells alone are able to support fetal development in the mouse. Development. 1990;110:815–21.
Horii T, Yamamoto M, Morita S, Kimura M, Nagao Y, Hatada I. P53 suppresses tetraploid development in mice. Sci Rep. 2015;5:8907.
Bowling S, di Gregorio A, Sancho M, Pozzi S, Aarts M, Signore M, et al. P53 and mTOR signalling determine fitness selection through cell competition during early mouse embryonic development. Nat Commun. 2018;9:1763.
Zhang G, Xiea Y, Zhou Y, Xiang C, Chen L, Zhang C, et al. P53 pathway is involved in cell competition during mouse embryogenesis. Proc Natl Acad Sci USA. 2017;114:498–503.
Dejosez M, Ura H, Brandt VL, Zwaka TP. Safeguards for cell cooperation in mouse embryogenesis shown by genome-wide cheater screen. Science. 2013;341:1511–4.
Sancho M, Di-Gregorio A, George N, Pozzi S, Sánchez JM, Pernaute B, et al. Competitive interactions eliminate unfit embryonic stem cells at the onset of differentiation. Dev Cell. 2013;26:19–30.
Clavería C, Giovinazzo G, Sierra R, Torres M. Myc-driven endogenous cell competition in the early mammalian embryo. Nature. 2013;500:39–44.
Hashimoto M, Sasaki H. Epiblast formation by TEAD-YAP-dependent expression of pluripotency factors and competitive elimination of unspecified cells. Dev Cell. 2019;50:139–54.
Díaz-Díaz C, Fernandez de Manuel L, Jimenez-Carretero D, Montoya MC, Clavería C, Torres M. Pluripotency surveillance by Myc-driven competitive elimination of differentiating cells. Dev Cell. 2017;4:585–99.
Ellis SJ, Gomez NC, Levorse J, Mertz AF, Ge Y, Fuchs E. Distinct modes of cell competition shape mammalian tissue morphogenesis. Nature. 2019;569:497–502.
Mesa KR, Rompolas P, Zito G, Myung P, Sun TY, Brown S, et al. Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool. Nature. 2015;522:94–97.
Lima A, Lubatti G, Burgstaller J, Hu D, Green AP, di Gregorio A, et al. Cell competition acts as a purifying selection to eliminate cells with mitochondrial defects during early mouse development. Nat Metab. 2021;3:1091–108.
Telang S, Lane AN, Nelson KK, Arumugam S, Chesney J. The oncoprotein H-RasV12 increases mitochondrial metabolism. Mol Cancer. 2007;6:77.
Jam FA, Morimune T, Tsukamura A, Tano A, Tanaka Y, Mori Y, et al. Neuroepithelial cell competition triggers loss of cellular juvenescence. Sci Rep. 2020;10:18044.
Kucinski I, Dinan M, Kolahgar G, Piddini E. Chronic activation of JNK JAK/STAT and oxidative stress signalling causes the loser cell status. Nat Commun. 2017;8:136.
Nagata R, Nakamura M, Sanaki Y, Igaki T. Cell competition is driven by autophagy. Dev Cell. 2019;51:99–112.
Baumgartner ME, Dinan MP, Langton PF, Kucinski I, Piddini E. Proteotoxic stress is a driver of the loser status and cell competition. Nat Cell Biol. 2021;23:136–46.
Recasens-Alvarez C, Alexandre C, Kirkpatrick J, Nojima H, Huels DJ, Snijders AP, et al. Ribosomopathy-associated mutations cause proteotoxic stress that is alleviated by TOR inhibition. Nat Cell Biol. 2021;23:127–35.
Langton PF, Baumgartner ME, Logeay R, Piddini E. Xrp1 and Irbp18 trigger a feed-forward loop of proteotoxic stress to induce the loser status. PLoS Genet. 2021;17:e1009946.
Lee CH, Kiparaki M, Blanco J, Folgado V, Ji Z, Kumar A, et al. A regulatory response to ribosomal protein mutations controls translation, growth, and cell competition. Dev Cell. 2018;46:456–69.
Baillon L, Germani F, Rockel C, Hilchenbach J, Basler K. Xrp1 is a transcription factor required for cell competition-driven elimination of loser cells. Sci Rep. 2018;8:17712.
Ochi N, Nakamura M, Nagata R, Wakasa N, Nakano R, Igaki T. Cell competition is driven by Xrp1-mediated phosphorylation of eukaryotic initiation factor 2α. PLoS Genet. 2021;17:e1009958.
Kiparaki M, Khan C, Folgado-Marco V, Chuen J, Moulos P, Baker NE. The transcription factor Xrp1 orchestrates both reduced translation and cell competition upon defective ribosome assembly or function. Elife 2022;11:e71705.
Ji Z, Chuen J, Kiparaki M, Baker N. Cell competition removes segmental aneuploid cells from drosophila imaginal disc-derived tissues based on ribosomal protein gene dose. Elife. 2021;10:e61172.
Tseng CY, Burel M, Cammer M, Harsh S, Flaherty MS, Baumgartner S, et al. chinmo-mutant spermatogonial stem cells cause mitotic drive by evicting non-mutant neighbors from the niche. Dev Cell. 2022;57:80–94.
Marusyk A, Porter CC, Zaberezhnyy V, DeGregori J. Irradiation selects for p53-deficient hematopoietic progenitors. PLoS Biol. 2010;8:e1000324.
Bondar T, Medzhitov R. p53-Mediated hematopoietic stem and progenitor cell competition. Cell Stem Cell. 2010;6:309–22.
Watanabe H, Ishibashi K, Mano H, Kitamoto S, Sato N, Hoshiba K, et al. Mutant p53-expressing cells undergo necroptosis via cell competition with the neighboring normal epithelial cells. Cell Rep. 2018;23:3721–9.
Norman M, Wisniewska KA, Lawrenson K, Pablo GM, Tada M, Kajita M, et al. Loss of scribble causes cell competition in mammalian cells. J Cell Sci. 2012;125:59–66.
Wagstaff L, Goschorska M, Kozyrska K, Duclos G, Kucinski I, Chessel A, et al. Mechanical cell competition kills cells via induction of lethal p53 levels. Nat Commun. 2016;7:11373.
Blanpain C, Fuchs E. Epidermal homeostasis: a balancing act of stem cells in the skin. Nat Rev Mol Cell Biol. 2009;10:207–17.
Mascré G, Dekoninck S, Drogat B, Youssef KK, Brohée S, Sotiropoulou PA, et al. Distinct contribution of stem and progenitor cells to epidermal maintenance. Nature. 2012;489:257–62.
Kato T, Liu N, Morinaga H, Asakawa K, Muraguchi T, Muroyama Y, et al. Dynamic stem cell selection safeguards the genomic integrity of the epidermis. Dev Cell. 2021;56:3309–20.
Liu N, Matsumura H, Kato T, Ichinose S, Takada A, Namiki T, et al. Stem cell competition orchestrates skin homeostasis and ageing. Nature. 2019;568:344–50.
Penzo-Méndez AI, Chen YJ, Li J, Witze ES, Stanger BZ. Spontaneous cell competition in immortalized mammalian cell lines. PLoS ONE. 2015;10:e0132437.
Colom B, Herms A, Hall MWJ, Dentro SC, King C, Sood RK, et al. Mutant clones in normal epithelium outcompete and eliminate emerging tumours. Nature. 2021;598:510–4.
Brown S, Pineda CM, Xin T, Boucher J, Suozzi KC, Park S, et al. Correction of aberrant growth preserves tissue homeostasis. Nature 2017;548:334–7.
Moya IM, Castaldo SA, van den Mooter L, Soheily S, Sansores-Garcia L, Jacobs J, et al. Peritumoral activation of the Hippo pathway effectors YAP and TAZ suppresses liver cancer in mice. Science. 2019;336:1029–34.
Martins VC, Busch K, Juraeva D, Blum C, Ludwig C, Rasche V, et al. Cell competition is a tumour suppressor mechanism in the thymus. Nature. 2014;509:465–70.
Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126:9–16.
Martincorena I, Campbell P. Somatic mutation in cancer and normal cells. Science. 2015;349:1478–83.
Martincorena I, Fowler JC, Wabik A, Lawson ARJ, Abascal F, Hall MWJ, et al. Somatic mutant clones colonize the human esophagus with age. Science. 2018;362:911–7.
Yizhak K, Aguet F, Kim J, Hess JM, Kübler K, Grimsby J, et al. RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues. Science. 2019;364:eaaw0726.
Kajita M, Fujita Y. EDAC: Epithelial defence against cancer - cell competition between normal and transformed epithelial cells in mammals. J Biochem. 2015;158:15–23.
Kajita M, Sugimura K, Ohoka A, Burden J, Suganuma H, Ikegawa M, et al. Filamin acts as a key regulator in epithelial defence against transformed cells. Nat Commun. 2014;5:4428.
Cho M, Thompson D, Cramer C, Vidmar T, Scieszka J. The Madin Darby canine kidney (MDCK) epithelial cell monolayer as a model cellular transport barrier. Pharm Res. 1989;6:71–7.
Hogan C, Dupré-Crochet S, Norman M, Kajita M, Zimmermann C, Pelling AE, et al. Characterization of the interface between normal and transformed epithelial cells. Nat Cell Biol. 2009;11:460–7.
Kajita M, Hogan C, Harris AR, Dupre-Crochet S, Itasaki N, Kawakami K, et al. Interaction with surrounding normal epithelial cells influences signalling pathways and behaviour of Src-transformed cells. J Cell Sci. 2010;123:171–80.
Leung CT, Brugge JS. Outgrowth of single oncogene-expressing cells from suppressive epithelial environments. Nature. 2012;482:410–3.
Chiba T, Ishihara E, Miyamura N, Narumi R, Kajita M, Fujita Y, et al. MDCK cells expressing constitutively active Yes-associated protein (YAP) undergo apical extrusion depending on neighboring cell status. Sci Rep. 2016;6:28383.
Tamori Y, Bialucha CU, Tian AG, Kajita M, Huang YC, Norman M, et al. Involvement of Lgl and mahjong/VprBP in cell competition. PLoS Biol. 2010;8:e1000422.
Ohoka A, Kajita M, Ikenouchi J, Yako Y, Kitamoto S, Kon S, et al. EPLIN is a crucial regulator for extrusion of RasV12- transformed cells. J Cell Sci. 2015;128:781–9.
Tanimura N, Fujita Y. Epithelial defense against cancer (EDAC). Semin Cancer Biol. 2020;63:44–48.
Kon S, Ishibashi K, Katoh H, Kitamoto S, Shirai T, Tanaka S, et al. Cell Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes. Nat Cell Biol. 2017;19:530–41.
Akter E, Tasaki Y, Mori Y, Nakai K, Hachiya K, Lin H, et al. Non Non-degradable autophagic vacuoles are indispensable for cell competition. Cell Rep. 2022;40:111292.
Menéndez J, Pérez-Garijo A, Calleja M, Morata G. A tumor-suppressing mechanism in Drosophila involving cell competition and the Hippo pathway. Proc Natl Acad Sci USA. 2010;107:14651–6.
Mamada H, Sato T, Ota M, Sasaki H. Cell competition in mouse NIH3T3 embryonic fibroblasts is controlled by the activity of Tead family proteins and Myc. J Cell Sci. 2015;128:790–803.
di Giacomo S, Sollazzo M, de Biase D, Ragazzi M, Bellosta P, Pession A, et al. Human cancer cells signal their competitive fitness through MYC activity. Sci Rep. 2017;7:12568.
Price CJ, Stavish D, Gokhale PJ, Stevenson BA, Sargeant S, Lacey J, et al. Genetically variant human pluripotent stem cells selectively eliminate wild-type counterparts through YAP-mediated cell competition. Dev Cell. 2021;56:2455–70.
van Neerven SM, de Groot NE, Nijman LE, Scicluna BP, van Driel MS, Lecca MC, et al. Apc-mutant cells act as supercompetitors in intestinal tumour initiation. Nature. 2021;594:436–41.
Pronobis MI, Rusan NM, Peifer M. A novel GSK3-regulated APC:Axin interaction regulates Wnt signaling by driving a catalytic cycle of efficient βcatenin destruction. Elife. 2015;4:e08022.
Krotenberg Garcia A, Fumagalli A, Le HQ, Jackstadt R, Lannagan TRM, Sansom OJ, et al. Active elimination of intestinal cells drives oncogenic growth in organoids. Cell Rep. 2021;36:109307.
Sasaki A, Nagatake T, Egami R, Gu G, Takigawa I, Ikeda W, et al. Obesity suppresses cell-competition-mediated apical elimination of RasV12-transformed cells from epithelial tissues. Cell Rep. 2018;23:974–82.
Slaughter DP, Southwick HW, Smejkal W. “Field cancerization” in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer. 1953;6:963–8.
Braakhuis BJM, Tabor MP, Kummer JA, Leemans CR, Brakenhoff RH. A genetic explanation of slaughter’s concept of field cancerization: evidence and clinical implications. Cancer Res. 2003;63:1723–30.
Aster JC, Pear WS, Blacklow SC. The varied roles of Notch in cancer. Annu Rev Pathol. 2017;12:245–75.
Alcolea MP, Greulich P, Wabik A, Frede J, Simons BD, Jones PH. Differentiation imbalance in single oesophageal progenitor cells causes clonal immortalization and field change. Nat Cell Biol. 2014;16:612–9.
Vermeulen L, Morrissey E, van der Heijden M, Nicholson AM, Sottoriva A, Buczacki S, et al. Defining stem cell dynamics in models of intestinal tumor initiation. Science. 2013;342:995–8.
Snippert HJ, Haegebarth A, Kasper M, Jaks V, van Es JH, Barker N, et al. Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science. 2010;327:1385–9.
Snippert HJ, Schepers AG, van Es JH, Simons BD, Clevers H. Biased competition between Lgr5 intestinal stem cells driven by oncogenic mutation induces clonal expansion. EMBO Rep. 2014;15:62–69.
Rhiner C, López-Gay JM, Soldini D, Casas-Tinto S, Martín FA, Lombardía L, et al. Flower forms an extracellular code that reveals the fitness of a cell to its neighbors in Drosophila. Dev Cell. 2010;18:985–98.
Merino MM, Rhiner C, Portela M, Moreno E. “Fitness fingerprints” mediate physiological culling of unwanted neurons in drosophila. Curr Biol. 2013;23:1300–9.
Merino MM, Rhiner C, Lopez-Gay JM, Buechel D, Hauert B, Moreno E. Elimination of unfit cells maintains tissue health and prolongs lifespan. Cell. 2015;160:461–76.
Moreno E, Fernandez-Marrero Y, Meyer P, Rhiner C. Brain regeneration in Drosophila involves comparison of neuronal fitness. Curr Biol. 2015;25:955–63.
Madan E, Pelham CJ, Nagane M, Parker TM, Canas-Marques R, Fazio K, et al. Flower isoforms promote competitive growth in cancer. Nature. 2019;572:260–4.
Overholtzer M, Mailleux AA, Mouneimne G, Normand G, Schnitt SJ, King RW, et al. A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion. Cell. 2007;131:966–79.
Li W, Baker NE. Engulfment is required for cell competition. Cell. 2007;129:1215–25.
Lolo FN, Casas-Tintó S, Moreno E. Cell competition time line: winners kill losers, which are extruded and engulfed by hemocytes. Cell Rep. 2012;2:526–39.
Bozkurt E, Düssmann H, Salvucci M, Cavanagh BL, van Schaeybroeck S, Longley D, et al. Trail signaling promotes entosis in colorectal cancer. J Cell Biol. 2021;220:e202010030.
Fadok PM, Voelker DR, Campbell PA, Cohen JJ. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol. 1992;148:2207–16.
Sun Q, Cibas ES, Huang H, Hodgson L, Overholtzer M. Induction of entosis by epithelial cadherin expression. Cell Res. 2014;24:1288–98.
Rizzotto D, Villunger A. P53 clears aneuploid cells by entosis. Cell Death Differ. 2021;28:818–20.
Mackay HL, Moore D, Hall C, Birkbak NJ, Jamal-Hanjani M, Karim SA, et al. Genomic instability in mutant p53 cancer cells upon entotic engulfment. Nat Commun. 2018;9:3070.
Lyng FM, Seymour CB, Mothersill C. Initiation of apoptosis in cells exposed to medium from the progeny of irradiated cells: a possible mechanism for bystander-induced genomic instability? Radiat Res. 2002;157:365–70.
Seymour CB, Mothersill C. Relative contribution of bystander and targeted cell killing to the low-dose region of the radiation dose-response curve. Radiat Res. 2000;153:508–11.
Pérez-Garijo A, Fuchs Y, Steller H. Apoptotic cells can induce non-autonomous apoptosis through the TNF pathway. Elife. 2013;2013:e01004.
Haynie JL, Bryant PJ. The effects of X-rays on the proliferation dynamics of cells in the imaginal wing disc of Drosophila melanogaster. Wilehm Roux’s Arch Dev Biol. 1977;183:85–100.
Pérez-Garijo A, Martín FA, Morata G. Caspase inhibition during apoptosis causes abnormal signalling and developmental aberrations in Drosophila. Development. 2004;131:5591–8.
Ryoo HD, Gorenc T, Steller H. Apoptotic cells can induce compensatory cell proliferation through the JNK and the wingless signaling pathways. Dev Cell. 2004;7:491–501.
Huh JR, Guo M, Hay BA. Compensatory proliferation induced by cell death in the Drosophila wing disc requires activity of the apical cell death caspase Dronc in a nonapoptotic role. Curr Biol. 2004;14:1262–6.
Tamori Y, Deng WM. Tissue repair through cell competition and compensatory cellular hypertrophy in postmitotic epithelia. Dev Cell. 2013;25:350–63.
Ballesteros-Arias L, Saavedra V, Morata G. Cell competition may function either as tumour-suppressing or as tumour-stimulating factor in Drosophila. Oncogene. 2014;33:4377–84.
Harrison DE. Competitive repopulation: a new assay for long-term stem cell functional capacity. Blood. 1980;55:77–81.
Shinohara T, Orwig KE, Avarbock MR, Brinster RL. Germ line stem cell competition in postnatal mouse testes 1. Biol Reprod. 2002;66:1491–7.
Kanatsu-Shinohara M, Takashima S, Shinohara T. Transmission distortion by loss of p21 or p27 cyclin-dependent kinase inhibitors following competitive spermatogonial transplantation. Proc Natl Acad Sci USA. 2010;107:6210–5.
Smith-Berdan S, Nguyen A, Hassanein D, Zimmer M, Ugarte F, Ciriza J, et al. Robo4 cooperates with Cxcr4 to specify hematopoietic stem cell localization to bone marrow niches. Cell Stem Cell. 2011;8:72–83.
Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T, et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science. 1999;283:845–8.
Umemoto T, Yamato M, Ishihara J, Shiratsuchi Y, Utsumi M, Morita Y, et al. Integrin-v3 regulates thrombopoietin-mediated maintenance of hematopoietic stem cells. Blood. 2012;119:83–94.
Yoshihara H, Arai F, Hosokawa K, Hagiwara T, Takubo K, Nakamura Y, et al. Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell. 2007;1:685–97.
Wang Z, Li G, Tse W, Bunting KD. Conditional deletion of STAT5 in adult mouse hematopoietic stem cells causes loss of quiescence and permits efficient nonablative stem cell replacement. Blood. 2008;113:4856–65.
Oertel M, Menthena A, Dabeva MD, Shafritz DA. Cell competition leads to a high level of normal liver reconstitution by transplanted fetal liver stem/progenitor cells. Gastroenterology. 2006;130:507–20.
Menthena A, Koehler CI, Sandhu JS, Yovchev MI, Hurston E, Shafritz DA, et al. Activin A, p15INK4b signaling, and cell competition promote stem/progenitor cell repopulation of livers in aging rats. Gastroenterology. 2011;140:1009–1020.
Schwall R, Robbins K, Jardieu P, Chang L, Lai C, Terrell T. Activin induces cell death in hepatocytes in vivo and in vitro. Hepatology. 1993;18:347–56.
Hully JR, Chang L, Schwall RH, Widmer RH, Terrell TG. Induction of apoptosis in the murine liver with recombinant human activin A. Hepatology. 1994;4:854–62.
Ding J, Yannam GR, Roy-Chowdhury N, Hidvegi T, Basma H, Rennard SI, et al. Spontaneous hepatic repopulation in transgenic mice expressing mutant human α1-antitrypsin by wild-type donor hepatocytes. J Clin Investig. 2011;121:1930–4.
Zheng C, Hu Y, Sakurai M, Pinzon-Arteaga CA, Li J, Wei Y, et al. Cell competition constitutes a barrier for interspecies chimerism. Nature. 2021;592:272–6.
Villa del Campo C, Clavería C, Sierra R, Torres M. Cell competition promotes phenotypically silent cardiomyocyte replacement in the mammalian heart. Cell Rep. 2014;8:1741–51.
Yamauchi H, Matsumaru T, Morita T, Ishikawa S, Maenaka K, Takigawa I, et al. The cell competition-based high-throughput screening identifies small compounds that promote the elimination of RasV12-transformed cells from epithelia. Sci Rep. 2015;5:15336.
Fernandez-Antoran D, Piedrafita G, Murai K, Ong SH, Herms A, Frezza C, et al. Outcompeting p53-mutant cells in the normal esophagus by redox manipulation. Cell Stem Cell. 2019;25:329–41.
Bruens L, Ellenbroek SIJ, Suijkerbuijk SJE, Azkanaz M, Hale AJ, Toonen P, et al. Calorie restriction increases the number of competing stem cells and decreases mutation retention in the intestine. Cell Rep. 2020;32:107937.
We apologize to colleagues whose contributions we could not adequately cite due to space constraints. We thank Fuchs lab members for helpful discussion and input. Figures and graphical abstract were generated using BioRender.
YF was supported by the EMBO Young Investigator program, ICRF (15-771-RCDA) grants, ISF individual 2124/19, and IPMP 1019045 2029637 grants, and ICRF acceleration AG-17-917.
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Yusupova, M., Fuchs, Y. To not love thy neighbor: mechanisms of cell competition in stem cells and beyond. Cell Death Differ 30, 979–991 (2023). https://doi.org/10.1038/s41418-023-01114-3