Stem Cell Niche Structure and Function

ANRV255-CB21-25ARI8September200517:11StemCellNiche:StructureandFunctionLinhengLiandTingXieStowersInstituteforMedicalResearch,KansasCity,Missouri64110;email:[e-mail],[e-mail].2005.21:605–31FirstpublishedonlineasaReviewinAdvanceonJuly1,2005TheAnnualReviewofCellandDevelopmentalBiologyisonlineat
2005byAnnualReviews.Allrightsreserved1081-0706/05/1110-0605$20.00KeyWordsadultstemcell,self-renewal,differentiation,multipotentiality,signalingAbstractAdulttissue-specificstemcellshavethecapacitytoself-renewandgeneratefunctionaldifferentiatedcellsthatreplenishlostcellsthroughoutanorganism’slifetime.Studiesonstemcellsfromdi-versesystemshaveshownthatstemcellfunctioniscontrolledbyextracellularcuesfromthenicheandbyintrinsicgeneticprogramswithinthestemcell.Here,wereviewtheremarkableprogressre-centlymadeinresearchregardingthestemcellniche.WecomparethedifferencesandcommonalitiesofdifferentstemcellnichesinDrosophilaovary/testisandCaenorhabditiselegansdistaltip,aswellasinmammalianbonemarrow,skin/hairfollicle,intestine,brain,andtestis.Onthebasisofthiscomparison,wesummarizethecommonfeatures,structure,andfunctionsofthestemcellnicheandhighlightimportantnichesignalsthatareconservedfromDrosophilatomam-mals.Wehopethiscomparativesummarydefinesthebasicelementsofthestemcellniche,providingguidingprinciplesforidentificationofthenicheinothersystemsandpointingtoareasforfuturestudies.605Annu.Rev.Cell.Dev.Biol.2005.21:605-631.Downloadedfromarjournals.annualreviews.orgbyStowersInstituteon10/11/05.Forpersonaluseonly.ANRV255-CB21-25ARI8September200517:11ContentsINTRODUCTION.................606StemCellBehaviorisRegulatedbyBothExtrinsicSignalsandIntrinsicPrograms.606TheHypothesisofandEvidencefortheStemCellNiche.......607STEMCELLNICHESINDROSOPHILAOVARYANDTESTIS.........................608GermLineStemCellandSomaticStemCellNichesintheDrosophilaOvary..............608TheGermLineStemCellNicheintheDrosophilaTestis.........610THEGERMLINESTEMCELLNICHEINC.ELEGANS........610KNOWNSTEMCELLNICHESINMAMMALIANSYSTEMS...613TheHematopoieticStemCellNiche.........................613TheEpithelialStemCellNicheinSkin........................615TheIntestinalStemCellNiche...617TheNeuralStemCellNiche.....618TheGermLineStemCellNicheinMice.......................619CONCLUSIONANDPROSPECTIVE.................622CommonFeatures,Structures,andFunctionsoftheStemCellNiche.........................622FUTUREDIRECTIONS...........622CellularandMolecularComponentsoftheStemCellNiche.........................623AsymmetricVersusSymmetricStemCellDivision............623StemCellMaintenanceandReversionfromCommittedDaughterCells................623NormalStemCellsandCancerStemCells:Niche-DependentorNiche-Independent.........623CLOSINGREMARKS.............624INTRODUCTIONStemCellBehaviorisRegulatedbyBothExtrinsicSignalsandIntrinsicProgramsStemcellsareasubsetofcellsthathavetheuniqueabilitytoreplenishthemselvesthroughself-renewalandthepotentialtodif-ferentiateintodifferenttypesofmaturecells.Thesecharacteristicsthereforeplayessentialrolesinorganogenesisduringembryonicde-velopmentandtissueregeneration.Therearetwomaintypesofstemcells:embryonicandadult.Thepluripotentembryonicstemcellisderivedfromtheinnercellmassofblas-tocystsandhastheabilitytogiverisetoallthreeembryonicgermlayers—ectoderm,en-doderm,andmesoderm(Chambers&Smith2004,Thomsonetal.1998).Asdevelopmentproceeds,theneedfororganogenesisarises,andtheembryoproperformsgermlinestemcells(GSCs)forreproductionandsomaticstemcells(SSCs)fororganogenesis.Althoughdiversified,GSCsandSSCsretainthefea-tureofself-renewal.Theyeitherareprogres-sivelyrestrictedindevelopment,givingrisetomultiplelineages(includingtissue-specificcells),orareunipotent,givingrisetosinglelineagecellsdestinedforcertaintissues(Fuchsetal.2004,Rossant2004,Weissman2000).Afterbirth,adultstemcells,includingbothGSCsandSSCs,resideinaspecialmicroenvi-ronmenttermedthe“niche,”whichvariesinnatureandlocationdependingonthetissuetype.Theseadultstemcellsareanessentialcomponentoftissuehomeostasis;theysup-portongoingtissueregeneration,replacingcellslostduetonaturalcelldeath(apoptosis)orinjury.Tosustainthisfunctionthrough-outtheorganism’slifespan,adelicatebalance606Li·XieAnnu.Rev.Cell.Dev.Biol.2005.21:605-631.Downloadedfromarjournals.annualreviews.orgbyStowersInstituteon10/11/05.Forpersonaluseonly.ANRV255-CB21-25ARI8September200517:11betweenself-renewalanddifferentiationmustbemaintained.Theunderlyingmechanismsthatcontrolthisdelicatebalancearefunda-mentaltounderstandingstemcellregulation,thenatureofcancer/tumorformation,andthetherapeuticuseofstemcellsinhumandisease.Therearevariousintrinsicprogramsthatcontrolstemcellself-renewalandpotency(Morrisonetal.1997).Forexample,HoxB4issufficienttoinduceandexpandhematopoi-eticstemcells(HSCs)whenintroducedintoembryonicstemcells(Kybaetal.2002,Sauvageauetal.1995).Bmi,amemberofthepolycombfamily,isrequiredforself-renewalofstemcellsinthehematopoieticandne