胚胎干细胞和成体干细胞标志物相关交流-蚂蚁淘在线

EmbryonicStemCellMarkers
HematopoieticStemCellMarkers
Mesenchymal/StromalStemCellMarkers
NeuralStemCellMarkers
References

Whilestemcellsarebestdefinedfunctionally,anumberofmolecularmarkershavebeenusedtocharacterizevariousstemcellpopulations.

Althoughfunctionshaveyettobeascertainedformanyoftheseearlymarkers,theiruniqueexpressionpatternandtimingprovideausefultoolforscientiststoinitiallyidentifyaswellasisolatestemcells.Thismini-reviewsummarizesevidenceregardingtherolesofspecificmarkersindefiningembryonic,hematopoietic,mesenchymal/stromal,andneuralstemcellpopulations.Formostofthemoleculesdiscussed,studiesperformedbothinvitroandinvivosupporttheirsignificantroleincharacterizingstemcells.Untilmoreisknownaboutthenovelmarker-negativestemcellpopulation,however,uncertaintystillexistsregardingthebenefitsofusingthesemarkersaloneorinvariouscombinationswhenidentifyingandisolatingcellsforstemcellresearch.

EmbryonicStemCellMarkers

Oct-4:Oct-4(alsotermedOct-3orOct3/4),oneofthePOUtranscriptionfactors,wasoriginallyidentifiedasaDNA-bindingproteinthatactivatesgenetranscriptionviaacis-elementcontainingoctamermotif.¹Itisexpressedintotipotentembryonicstemandgermcells.^2,3AcriticallevelofOct-4expressionisrequiredtosustainstemcellself-renewalandpluripotency.⁴Differentiationofembryonicstem(ES)cellsresultsindown-regulationofOct-4,aneventessentialforaproperanddivergentdevelopmentalprogram.⁵Oct-4isnotonlyamasterregulatorofpluripotencythatcontrolslineagecommitment,butisalsothefirstandmostrecognizedmarkerusedfortheidentificationoftotipotentEScells.

SSEAs(StageSpecificEmbryonicAntigens):SSEAswereoriginallyidentifiedbythreemonoclonalantibodies(Abs)recognizingdefinedcarbohydrateepitopesassociatedwithlacto-andglobo-seriesglycolipids,SSEA-1,-3and-4.⁶SSEA-1isexpressedonthesurfaceofpreimplantation-stagemurineembryos(i.e.attheeightcellstage)andhasbeenfoundonthesurfaceofteratocarcinomastemcells,butnotontheirdifferentiatedderivatives.^7,8Theoviductepithelium,endometriumandepididymis,aswellassomeareasofthebrainandkidneytubulesinadultmicehavealsobeenshowntobereactivewithSSEA-1Abs.⁹SSEA-3and-4aresynthesizedduringoogenesisandarepresentinthemembranesofoocytes,zygotesandearlycleavage-stageembryos.^10,11BIOLOGicalrolesofthesecarbohydrate-associatedmoleculeshavebeensuggestedincontrollingcellsurfaceinteractionsduringdevelopment.⁶UndifferentiatedprimateEScells,humanECandEScellsexpressSSEA-3andSSEA-4,butnotSSEA-1.UndifferentiatedmouseEScellsexpressSSEA-1,butnotSSEA-3orSSEA-4.^12,13

HematopoieticStemCellMarkers

CD34:ThecellsurfacesialomucinCD34

Figure1.AstructuremodelofCD133proposedbyMiragliaS.etal.30ThisproteinhasanextracellularN-terminus,5hydrophobictransmembranedomains,2smallcytoplasmicloops,2largeextracellularloopsandacytoplasmicC-termus.

hasbeenafocusofinteresteversinceitwasfoundexpressedonasmallfractionofhumanbonemarrowcells.¹⁴TheCD34⁺-enrichedcellpopulationfrommarrowormobilizedperipheralbloodappearsresponsIBLeformostofthehematopoieticactivity.^14-21CD34hasthereforebeenconsideredtobethemostcriticalmarkerforhematopoieticstemcells(HSCs).CD34expressiononprimitivecellsisdown-regulatedastheydifferentiateintomaturecells.²²ItisalsofoundonclonogenicProgenitors,however,andsomelineage-committedcells.²³Althoughitsprecisefunctionisstillunknown,thepatternofexpressionofCD34suggeststhatitplaysasignificantroleinearlyhematopoiesis.²²ThetheoryofCD34beingthemostprimitiveHSCmarker,however,hasrecentlybeenchallenged.Osawaetal.firstdemonstratedthatmurineHSCscouldbeCD34negative.²⁴Inaddition,alowlevelofengraftmentandhematopoieticcapacityhasbeendemonstratedinhumanCD34-cells.²⁵TransplantationstudiesalsoshowedrepopulatingactivityinaCD34-cellpopulationinfetalsheep.²⁶Additionally,studieshaveshownthatbothmurineandhumanCD34⁺cellsmaybederivedfromCD34-cells.^27,28Collectively,thesereportssuggestthepossibilitythatHSCsmaybeCD34⁺orCD34-andthatselectionofcellsexpressingCD34mightresultinexclusionofmoreprimitivestemcells.Nevertheless,almostallclinicalandexperimentalprotocolsincludingexvivoculture,genetherapy,andHSCtransplantationarecurrentlydesignedforcellpopulationsenrichedforCD34⁺cells.

Figure2.ThefamilyofABCtransportersischaracterizedbythepresenceofanATP-bindingcassetteregion,whichhydrolyzesATPtosupportenergy-dependentsubstrateexportationfromtheintracellularcytoplasmtotheextracellularspace.Full-lengthtransporterscontaintwomirrorimagehalvesthatareseparatedbyaflexiblelinkerregion(notshown).Half-transporters,e.g.ABCG2,functionashomo-orheterodimersandmaybelocalizedtotheplasmamembrane.

CD133:CD133,a120kDa,glycosylatedproteincontainingfivetransmembranedomains(Figure1),wasidentifiedinitiallybytheAC133monoclonalAb,whichrecognizesaCD34⁺subsetofhumanHSCs.^29,30ACD133isoform,AC133-2,hasbeenrecentlyclonedandidentifiedastheoriginalsurfaceantigenrecognizedbytheAC133Ab.³¹CD133mayprovideanalternativetoCD34forHSCselectionandexvivoexpansion.ACD133⁺enrichedsubsetcanbeexpandedinasimilarmannerasaCD34⁺enrichedsubset,retainingitsmultilineagecapacity.³²RecentstudieshaveofferedevidencethatCD133expressionisnotlimitedtoprimitivebloodcells,butdefinesuniquecellpopulationsinnon-hematopoietictissuesaswell.CD133⁺progenitorcellsfromperipheralbloodcanbeinducedtodifferentiateintoendothelialcellsinvitro.³³Inaddition,humanneuralstemcellscanbedirectlyisolatedbyusingananti-CD133Ab.³⁴

ABCG2:ABCG2(ATP-bindingcassettesuperfamilyGmember2)isadeterminantoftheHoechst-negativephenotypeofsidepopulation(SP)andfoundinawidevarietyofstemcells,includingHSC.^35,36ABCG2isamemberofthefamilyofABCtransportersandwasfirstidentifiedinabreastcancercellline.³⁷Itbelongstothehalf-transportergroupandisuniqueasitislocalizedtotheplasmamembrane(Figure2).³⁸TheexpressionofABCG2appearsgreatestonCD34-cellsandisdown-regulatedwiththeacquisitionofCD34onthecellsurface.³⁵Down-regulationinABCG2expressionisalsoobservedinvariouscommittedhematopoieticprogenitors.³⁹ABCG2maythereforeserveasamorepromisingmarkerthanCD34forprimitiveHSCisolationandcharacterization.TheexpressionpatternofABCG2,however,isnotlimitedtoHSC.ABCG2expressionexclusivelycharacterizestheHoechstSPphenotypeincellsfromdiversesources,includingmonkeybonemarrow,mouseskeletalmuscleandEScells.³⁵ThepotentialplasticityofSPcellshasbeendemonstratedbystudiesshowingthatcardiomyocytesandmusclecanberegeneratedfromtransplantedbonemarrow-derivedSPcells.^40,41ExclusiveexpressionofABCG2onSPcellssuggeststhatABCG2maybeapotentialmarkerforpositiveselectionofpluripotentstemcellsfromvariousadultsources.ABCG2hasbeenimplicatedinplayingafunctionalroleindevelopmentalstemcellbiology(seereference42forareview).

Sca-1:Sca-1(stemcellantigen1,Ly-6A/E),an18kDaphosphatidylinositol-anchoredprotein,isamemberoftheLy-6antigenfamily.⁴³Sca-1isthemostrecognizedHSCmarkerinmicewithbothLy-6haplotypesasitisexpressedonmultipotentHSCs.^44,45Ananti-Sca-1Abisfrequentlyusedincombinationwithnegativeselectionforexpressionofanumberofcellsurfacemarkerscharacteristicofdifferentiatedcellsofhematolymphoidlineages(Lin-)toidentifyandisolatemurineHSCs.Sca-1⁺HSCscanbefoundintheadultbonemarrow,fetalliverandmobilizedperipheralbloodandspleenwithintheadultanimal.^44-49Sca-1hasalsobeendiscoveredinseveralnon-hematopoietictissues,⁴³however,andcanbeusedtoenrichprogenitorcellpopulationsotherthanHSCs.⁵⁰Sca-1maybeinvolvedinregulatingbothBandTcellactivation.^51-54

Mesenchymal/StromalStemCellMarkers

STRO-1:ThemurineIgMmonoclonalAbSTRO-1,producedfromanimmunizationwithapopulationofhumanCD34⁺bonemarrowcells,canidentifyacellsurfaceantigenexpressedbystromalelementsinhumanbonemarrow.⁵⁵Frombonemarrowcells,thefrequencyoffibroblastcolony-formingcells(CFU-F)isenrichedapproximately100-foldintheSTRO-1⁺/GlycophorinA-populationthanintheSTRO-1⁺/GlycophorinA⁺population.⁵⁵ASTRO-1⁺enrichedsubsetofmarrowcellsiscapableofdifferentiatingintomultiplemesenchymallineagesincludinghematopoiesis-supportivestromalcellswithavascularsmoothmuscle-likephenotype,ADIpocytes,osteoblastsandchondrocytes.^56-59STRO-1isavaluableAbfortheidentification,isolationandfunctionalcharacterizationofhumanbonemarrowstromalcellprecursors,whicharequitedistinctfromthoseofprimitiveHSCs.

另外，还有这些marker:CD71,CD105,SH2.SH3,SH4

NeuralStemCellMarkers

Nestin:NestinisaclassVIintermediatefilamentprotein.^60,61Althoughitisexpressedpredominantlyinstemcellsofthecentralnervoussystem(CNS),⁶²itsexpressionisabsentfromnearlyallmatureCNScells.⁶³NestinhasbeenthemostextensivelyusedmarkertoidentifyCNSstemcellswithinvariousareasofthedevelopingnervoussystemandinculturedcellsinvitro.^34,64-68TheroleofnestininCNSstemcellbiology,however,remainsundefined.Althoughnestindoesnotformintermediatefilamentsbyitselfinvitroa-internexintoformhomo-andheterodimer,coiled-coilcomplexesthatmaythenformintermediatefilaments.⁶⁹Itstransientexpressionhasbeensuggestedtobeamajorstepintheneuraldifferentiationpathway.⁶¹Nestinexpressionhasalsobeendiscoveredinnon-neuralstemcellpopulations,suchaspancreaticisletprogenitors^70-72aswellashematopoieticprogenitors.⁷³

PSA-NCAM(Polysialicacid-neuralcelladhesionmolecule):Theregulatedexpressionofneuralcelladhesionmolecule(NCAM)isoformsinthebrainiscriticalformanyneuraldevelopmentalprocesses.TheembryonicformofNCAM,PSA-NCAM,ishighlypolysialylatedandismainlyexpressedinthedevelopingnervoussystem.⁷⁴PSA-NCAMmayberelatedtosynapticrearrangementandplasticity.⁷⁵Intheadult,PSA-NCAMexpressionisrestrictedtoregionsthatretainplasticity.⁷⁶Aneuronal-restrictedprecursoridentifiedbyitshighexpressionofPSA-NCAMcanundergoself-renewalanddifferentiateintomultipleneuronalphenotypes.⁷⁷PSA-NCAM⁺neonatalbrainprecursorsarerestrictedtoaglialfateandthyroidhormonecanmodulatethemintoanoligodendrocytefate.^78-80PolysialicacidmodificationsignificantlydecreasesNCAMadhesivenessandtherefore,itwasoriginallysuggestedPSA-NCAMworksasapurelyanti-adhesivefactorthatmodulatescell-cellinteractionsinpromotingbrainplasticity.IncreasingevidenceindicatesthatPSA-NCAMmayinteractwithsecretedsignalingmoleculestoperformaninstructiveroleindevelopment.^81,82

Figure3.ThestructureofNGFwithamodelofthep75NeurotrophinReceptor.Theextracellulardomainofthereceptoristakenfromthetumornecrosisfactorreceptorstructureandtheintracellularportioncontainsadeathdomain.

p75NeurotrophinR(NTR):p75NTR,alsonamedlowaffinitynervegrowthfactor(NGF)receptor,isatypeItransmembraneproteinthatbelongstothetumornecrosisfactorreceptorsuperfamily(Figure3).⁸³ItbindstoNGF,BDNF,NT-3andNT-4equally(withlowaffinity).p75NTR,whenactivatedinthepresenceofTrk,enhancesresponsestoneurotrophin(seereference84forareview).TrkCreceptorsworkingtogetherwithp75NTRhavebeensuggestedtoservecriticalfunctionsduringthedevelopmentofthenervoussystem.⁸⁵Neuralcreststemcells(NCSCs)havebeenisolatedbasedontheirsurfaceexpressionofp75NTR.^86,87Freshlyisolatedp75NTR⁺NCSCsfromperipheralnervetissuescanself-renewandgenerateneuronsandgliabothinvitroandinvivo.Inaddition,neuroepithelial-derivedp75NTR⁺cellsarealsoabletodifferentiateintoneurons,smoothmuscleandSchwanncellsinculture.⁸⁸Recently,p75NTRhasbeenusedasamarkertoidentifymesenchymalprecursorsaswellashepaticstellatecells.^89,90

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干细胞相关仪器试剂耗材

细胞培养皿
细胞培养系统
细胞计数
干细胞/祖细胞
干细胞培养基
干细胞分化干细胞扩增
干细胞鉴定
干细胞培养质控
干细胞培养添加物
干细胞培养附件
细胞因子、趋化因子和生长因子
细胞培养添加物
siRNA库

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