TheSoxFamilyofTranscriptionFactors:VersatileRegulatorsofStemandProgenitorCellFateAbbySarkar1,2,3andKonradHochedlinger1,2,3,#1HowardHughesMedicalInstituteatMassachusettsGeneralHospitalCancerCenterandCenterforRegenerativeMedicine,185CambridgeStreet,Boston,MA02114,USA2DepartmentofStemCellandRegenerativeBiology,HarvardUniversityandHarvardMedicalSchool,7DivinityAvenue,Cambridge,MA02138,USA3HarvardStemCellInstitute,1350MassachusettsAvenue,Cambridge,MA02138AbstractTheSoxfamilyoftranscriptionfactorsarewell-establishedregulatorsofcellfatedecisionsduringdevelopment.Accumulatingevidencedocumentsthattheyplayadditionalrolesinadulttissuehomeostasisandregeneration.Remarkably,forcedexpressionofSoxfactors,incombinationwithothersynergisticfactors,reprogramsdifferentiatedcellsintosomaticorpluripotentstemcells.DysregulationofSoxfactorshasbeenfurtherimplicatedindiseasesincludingcancer.Here,wereviewmolecularandfunctionalevidencelinkingSoxproteinswithstemcellbiology,cellularreprogramming,anddiseasewithanemphasisonSox2.IntroductionStemcellsarecharacterizedbythecapacitytocontinuouslyself-renewandthepotentialtodifferentiateintooneormorematurecellularlineages(SimonsandClevers,2011).Theyservetoformtissuesandorgansduringmammaliandevelopment,andtheymaintainongoingcellularturnoverandprovideregenerativecapacityincertainadulttissues.Onecandistinguishbetweenpluripotentembryonicstemcells(ESCs),whichgiverisetoallembryoniclineages,andsomaticstemcells,whichgiverisetooneormorespecializedlineageswithinthetissuestheyresidein.Astemcell’sdecisionforself-renewalordifferentiationisintrinsicallycontrolledbytheinterplayofcelltype-specifictranscriptionfactorsandchromatinregulators.Althoughseveralsuchmoleculeshavebeenimplicatedinstemcellbiologyoverthelastfewyears,themechanisticmodesofactionofthesemoleculesremainincompletelyunderstood.ResearchontheSoxgenefamilybeganwiththeseminaldiscoveryofthemammaliantestis-determiningfactor,Sry(Gubbayetal.,1990;Sinclairetal.,1990).Srycarriesacharacteristichigh-mobility-group(...
