ReviewEpigeneticRegulationofMesenchymalStemCellHomeostasisBing-DongSui,1,3Chen-XiZheng,1,3MengLi,1,3YanJin,1,*andCheng-HuHu2,*Mesenchymalstemcells(MSCs)haveputativerolesinmaintainingadulttissuehealth,andthefunctionaldeclineofMSCshasemergedasacrucialpathophysiologicaldriverofvariousdis-eases.EpigeneticregulationisessentialforestablishingandpreservingMSChomeostasisinvivo.Furthermore,growingevidencesuggeststhatepigeneticdysregulationcontributestoage-anddisease-associatedMSCalterations.EpigeneticmarksinMSCscanbeamplifiedthroughself-renewaldivisionsandtransmittedtodifferentiatedprogeny,furtherperpetuatingtheirroleintissuemaintenanceandpathogenesis.WereviewtheepigeneticregulationofMSChomeostasis,emphasizingitscontributionstoorganismalhealthanddisease.UnderstandingtheseepigeneticmechanismscouldholdpromiseastargetsforMSC-mediatedregenerativetherapies.MSCsinTissueHealthandDiseaseMSCsareheterogeneous,primitivecellsthatwereoriginallydiscoveredinadultbonemarrowstroma.SincethenMSCshavebeenshowntobeubiquitousindiversetissues[1,2].MSCspossessself-renewal(seeGlossary)andmultidifferentiationpotential,andhaveextensiveanddynamicinter-actionswiththestemcellniche.MSCsareincreasinglyrecognizedascrucialcontributorstohomeo-stasisandregenerativerepairoftissuesandorgansderivedfromthemesoderm,ectoderm,andendoderm[3–6](Box1).Furthermore,accumulatingevidencesuggeststhatdisordersofMSCs,includingimpairedproliferation,biaseddifferentiation,anddysfunctionalnichemodulation,underlietissuealterationsinagingandindisease[7–9].AlthoughthefunctionofMSCsintissuehealthanddiseaseiswellrecognized,theregulatorymech-anismsofMSCbehaviorsinvivoremainlessdefined.Inrecentyears,epigeneticregulation(Box2)hasemergedasasignificantcontributortostemcell-mediatedtissuemaintenance[10,11].Inparticular,epigeneticmechanismsorchestrateMSCfatedecisionsandpreserveMSChomeostasisinvivo[12–15],whereasepigeneticdysregulationcanleadtoaberrationsinMSCfunctions[16–18](Table1,KeyTable).Notably,epigeneticmarksinMSCscanbeamplifiedd...
