Fromtotipotencyofzygotestopluripotencyintheblas-tomereandmultipotency,oligopotencyorunipotencyinmaturetissues,self-renewingstemcells(SCs)becomeincreasinglyrestrictedintheircellfateoptions.Inadulthumans,the50–70billioncellslostdailyintissuesfromwearandteararereplenishedthroughtheactionoflineage-restricted,residentSCs,whichactasguardiansoftheirdesignatedlineagesthroughoutlife(BOX1).Thisprocessofsteady-statetissuemaintenanceisknownashomeostasisandisoneofthemostcrucialrolesofatissueSC.Inaddition,tissueSCsmustbeequippedtorapidlybolstertheirregenerativeresponseandrestoretissueintegritywhenwounded,aprocessvitalfortheorgan-ism.Eventhoughregenerativecapacityvariesmarkedlyacrossdifferenttissues—forexample,theskinandtheheartrepresentthetwoextremesofhighandlowregen-erationability,respectively—theirsenseofurgencytorepairwoundsisconservedandhascapturedthemolecularresourcefulnessofnature.Theoutcomeisabroadeningofregenerativepowersandlineageoptionscomparedwiththoseseenundernormalhomeostasis.ByenablingSCstoembarkuponbehavioursthataredistinctfromtheirnormalpatternsunderhomeostasis,aphenomenontermedcellplasticity,theSCsclosesttoawoundcanparticipateinrepairingit,therebyheight-eningthechancesoftissuerestorationandorganismsurvival.However,asanessentialsurvivalmechanismduringwoundrepair,plasticityisoftenhijackedbycan-cer,bypassingtheneedforactualinjuryinthepresenceofaccumulatingoncogenicmutations.Manyparallelsexistbetweenwoundsandcancer,withafewfeaturesdistinguishingthetwophenomena.ThisReviewdiscussesSCplasticityinthecontextofnormaltissuesasSCstransitionfromhomeostasistowoundrepairandtacklesplasticityinmalignantpro-gression,awound-healingprocessgoneamok.WeaimtocontrastSCbehavioursundersteadystatetothosethatareunderstress.Meanwhile,wedrawanalogiesacrossdiversestressconditions,includingwounding,transplantation,cultureandcancer,toillustratehowSCplasticityisconservedincertainaspectsanddistinctinothers.WefocusonplasticityinthecontextofSCs;however,theabilitytoremodelbehaviourinresponsetoc...
