stem cell course-Wenzhou-2017PPT课件.pptx

stem cell course-Wenzhou-2017PPT课件.pptx

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1.BasicKnowledgesaboutStemCells,（,干细胞基本知识）DefinitionClassificationCharacterizationStemCellsinTestis（睾丸干细胞）GermlinestemcellsSomaticstemcellsStemCellsinOvary（卵巢干细胞）GermlinestemcellsSomaticstemcellsFutureDirections（未来方向）Germlinestemcells-physiologicalrelevant?

Assistantreproductionwithinducedoocytes?

本课内容,Self-renewaltomaintainthemselves（自我增殖）Differentiationtoformspecializedcells（分化成子代细胞）,Whatarestemcells?

Stemcellsarethecellsthatcandivideessentiallywithoutlimittoformothercells.（无限分裂并形成其他细胞的细胞）,全能干细胞（Totipotentstemcells）:

Cellscanformallthecelltypesinabody,plustheextraembryonic,orplacental,cells.Embryoniccellswithinthefirstcoupleofcelldivisionsafterfertilizationaretheonlycellsthataretotipotent（包括胎盘）.多能干细胞（Pluripotentstemcells）:

Cellscangiverisetoallofthecelltypesthatmakeupthebody;embryonicstemcellsareconsideredpluripotent（不包括胎盘）.亚多能干细胞（Multipotentstemcells）:

Cellscandevelopintomorethanonecelltype,butaremorelimitedthanpluripotentcells;adultstemcellsandcordbloodstemcellsareconsideredmultipotent.单能干细胞（Unipotentstemcells）:

Cellreferstoacellthatcandifferentiatealongonlyonelineage.,干细胞的多能性,Totipotent,滋养层,囊胚,Multipotentstemcells（亚多能干细胞）,骨髓祖细胞,淋巴祖细胞,Embryonicstemcells（胚胎干细胞）Generatedfromcellsofapreimplantation-stageembryoTotipotentPluripotent“Somatic”or“adult”stemcells（成体干细胞）Generatedfromdevelopingorwell-developedoradultorgansMultipotentUnipotentInducedpluripotentstemcells（iPSCs）（诱导多潜能干细胞）Generatedfromtransductionof4transcriptionalfactors（Oct4（Pou5f1）,Sox2,cMyc,andKlf4）Pluripotent,Classification（分类）,干细胞小巢及干细胞对称性和非对称性分裂,干细胞小巢Stem-cellniche,Thespecificanatomiclocationwherestemcellslive,whichcontainsextracelluarmatrixandregulatorycells.Theniche（home）playsimportantrolesindeterminingstemcellsfate.Thewordnicheoftenbereferedtoasstem-cellmicroenvironmentinvivoorinvitro.小巢是指干细胞“生活”的位置，其中包含细胞外基质和调控细胞。

小巢（家）在调控干细胞的活动及确定干细胞的命运中起着重要的作用。

“小巢”一词通常被泛指体内或体外干细胞生存的微环境。

“归巢”是指干细胞从身体的其它位置，向其小巢回归的过程。

BasicKnowledgesaboutStemCellsDefinitionClassificationCharacterizationStemCellsinTestisGermlinestemcellsSomaticstemcellsStemCellsinOvaryGermlinestemcellsSomaticstemcellsFutureDirectionsGermlinestemcells-physiologicalrelevant?

Assistantreproductionwithinducedoocytes?

本课内容,SPERMATOGENESIS:

https:

/,曲细精管,间质,GermcellsSertolicellsLeydigcellsMyoidcellsMacrophagesBloodvessels,SPERMATOGENESIS:

https:

/,https:

/,DifferencesBetweenRodentsandHuman,M,O,U,ES,H,MU,A,N,Gfra1,c-Kit,ID4PAX7BMI1,TheAsmodelforspermatogonialmultiplicationandstemcellrenewal.,DirkG.deRooijDevelopment2017;144:

3022-3030,2017.PublishedbyTheCompanyofBiologistsLtd,简单模型,Thefragmentationmodelforspermatogonialmultiplicationandstemcellrenewal.,DirkG.deRooijDevelopment2017;144:

3022-3030,2017.PublishedbyTheCompanyofBiologistsLtd,碎片模型,ThehierarchicalAsmodel.,DirkG.deRooijDevelopment2017;144:

3022-3030,2017.PublishedbyTheCompanyofBiologistsLtd,分级模型,Gfra1,C-Kit,Spermatogoniastemcellmarkers,TruestemmarkersID4:

inhibitorofdifferentiation4PAX7:

pairedbox7BMI1:

Bcell-specificMoloneymurineleukaemiavirusintegrationsite1DifferentatingmarkersNgn3:

neurogenin3Gfra1:

GDNFfamilyreceptoralpha1Fbxw7:

Skp1-Cullin-F-box（SCF）-typeubiquitinligase,SummarySpermatogoniastemcells,Highturnovercells,activeduringtheindividualslifetimeNumberoftheprogeniescanbegeneratedbyeachstemcellarelimitedRodentsgenerate500foldsofgermcellsthanhumanforeachstemcelldivisionThreemodelshavebeenproposedbywhichhowspermatogoniastemcellsundergodifferentiation:

Asmodel（简单模型）;Fragmentationmodel（碎片模型）;Hierarchicalmodel（分级模型）。

TesticularStemCellsforSomaticcells,Sertolicells?

（notyet）Myiodcells?

（notyet）Leydigcells?

Yes（PeritubularandPerivescularlocations）,CD90,绿色-管周细胞（smactin）,红色间质细胞（P450scc）,培养4周后，在管周myoid细胞的外表面，出现间质细胞,BasicKnowledgesaboutStemCellsDefinitionClassificationCharacterizationStemCellsinTestisGermlinestemcellsSomaticstemcellsStemCellsinOvaryGermlinestemcellsSomaticstemcellsFutureDirectionsGermlinestemcells-physiologicalrelevant?

Assistantreproductionwithinducedoocytes?

本课内容,植物根尖生长（干细胞功能及顶尖生长）,低等动物的卵巢含有生殖干细胞Celegans线虫（含生殖干细胞）,Drosophila果蝇（含生殖干细胞）,Medaka日本淡水鱼（含生殖干细胞）,哺乳动物卵巢含有生殖干细胞吗？

传统的观点：

卵巢不含生殖干细胞Eggnumberislimitedandcouldbedepletedbyageof50,JonathanL.Tilly,2004哺乳动物成年卵巢含有生殖干细胞,（GermlineStemCells:

GSC）JonathanL.TillyGroupNature2004;428:

14550.1.Countingatreticfollicles（33%immaturefolliclesareatretic,whichcouldresultindepletionoffolliclesmuchearlier）（卵泡萎缩速度太快）GermcellmarkersVasahomologue（MVH,aksDeadbox4,orDDX4）andsynaptonemalcomplexprotein3（SCP3）-positivecellswerefoundatovariansurfaceepithelium（previouslytermedgerminalepithelium）.BrdUincorporationofMVH-positivecells（卵泡外表达生殖细胞基因的细胞）Germcelltoxicant（busulfan）onlyaffectedfolliclein2weeks,suggestingitaffectedGSC（毒物影响卵泡的速度太慢）OccurrenceofGFP-expressingoocytessurroundedbynon-GFPovariescellsaftertransplantationofGFPovarytissue（卵巢细胞移植）,哺乳动物成年卵巢不含有生殖干细胞,（GermlineStemCells:

GSC）,？

JonathanL.TillyGroupNature2004;428:

14550.,GosdenRG.HumanitRepUpdate2004;10:

1935.GreenfeldC,FlawsJA.Bioessays2004;26:

82932.ByskovAG,FaddyMJ,LemmenJG,AndersenCY.Eggsforever?

Differentiation2005;73:

43846.Bristol-GouldSK,KreegerPK,SelkirkCG,KilenSM,MayoKE,SheaLD,etal.DevBiol2006;298:

14954.JohnGB,ShirleyLJ,GallardoTD,CastrillonDG.Reproduction2007;133:

85563.MottaPM,MakabeS.JSubmicroscCytol1986;18:

27190.AlbertiniDF.Reproduction2004;127:

5134.,骨髓干细胞可以补充卵巢干细胞（2005）OocyteGenerationinAdultMammalianOvariesbyPutativeGermCellsinBoneMarrowandPeripheralBlood；Cell.122,2005,Pages303315,Folliclenumberrecovered2monthsafterdepleteovarianfolliclesbychemotherapydrug（化疗两个月后卵泡数量会恢复）CD51-positiveprimordialgermcellsexpressgermlinemakersOct4,Mvh,Dazl,andStella,butnotoocytemarkers,Gdf9orZp3.Thesemarkerswerealsofoundinbonemarrow.（早期原始生殖细胞跟骨髓干细胞表达一些相似的基因）MicetreatedwithcyclophosphamideandbusulfantodestroyexistingGSCsthatalsoreceivedbonemarrowtransplantshadareturnofoocyte-containingfollicles.（化疗动物接受骨髓移植后，卵泡会比没有骨髓移植动物恢复的快）PeripheralbloodfromGFPmicetoAtm-deficientmiceresultedGFP-positiveoocytesweredetectableinrecipientsovary（输血动物可以在其卵巢中看到GFP标记的来自供血动物的卵泡细胞）,骨髓干细胞可以补充卵巢干细胞OocyteGenerationinAdultMammalianOvariesbyPutativeGermCellsinBoneMarrowandPeripheralBlood；Cell.122,2005,Pages303315,合体实验,2009卵巢生殖干细胞的分离,中国上海交大SchoolofLifeScienceandBiotechnology,ShanghaiJiaoTongUniversity,Shanghai,200240,China.FACSisolationofMVH/DDX4-expressingcellsMVH（mousevasahomologueprotein）DDX4（DEADboxpolypeptide4）ZouK,YuanZ,YangZ,LuoH,SunK,ZhouL,etal.Productionofoffspringfromagermlinestemcelllinederivedfromneonatalovaries.NatCellBiol2009;11:

6316.,b:

Red,BrdU-positivecells.（c）ArrowsindicateMVH+cells.（e）BrdU（green）andMVH（red）,争论在继续。

WheredoOogonialstemcellslocate?

germinativeepithelium（GE）Ovariancortex,卵巢生殖干细胞的位置？

Structureoftheovary.Thecorticalregionissurroundedbyasimpleepitheliumclassicallynamedgerminativeepithelium（GE）.Underlyingtheovariansurfaceepitheliumisaconnectivetissuelayer,thetunicaalbuginea（TA）.Groupsofprimordialfollicles（PF）arepresentintheovarianstroma.ColHEstainx40.,Marker蛋白的特异性？

生理意义？

NotyetYes,Yes,卵巢含有体细胞系列的干细胞吗？

Somaticstemcellsintheovary?

1.BasicKnowledgeofStemCells,DefinitionClassificationCharacterizationStemCellsinTestisGermlinestemcellsSomaticstemcellsStemCellsinOvaryGermlinestemcellsSomaticstemcellsFutureDirectionsGermlinestemcells-physiologicalrelevant?

Assistantreproductionwithgermlineandsomaticstemcells?

外源性（体细胞系列）的干细胞可以帮助卵巢功能恢复,Niche功能？

Yes转化成生殖干细胞？

Noconvincingevidence,子宫内膜间充质干细胞,脐带间充质干细胞,骨髓间充质干细胞,BasicKnowledgeofStemCellsDefinition（永久再生并形成其他细胞）Classification（胚胎，组织，诱导）Characterization（全能，多能，亚多能，单能）Niche（小巢）StemCellsinTestisGermlinestemcells（精原干细胞）Somaticstemcells（间质干细胞，其他未知！

）StemCellsinOvaryGermlinestemcells（可能，极大争议）Somaticstemcells（卵巢外表皮细胞，thecacell，粒细胞？

）FutureDirectionsGermlinestemcells-physiologicalrelevant?

（生理意义不明）Assistantreproductionwithgermlineandsomaticstemcells?

（可能）子宫内膜间充质干细胞;脐带间充质干细胞;骨髓间充质干细胞,总结,1.,干细胞的分类及各类的特性（胚胎，成年/组织，诱导）（全能，多能，亚多能，单能）,2.,精原干细胞自我增殖及分化的三个模型（简单，碎片，分级）,3.,卵巢干细胞的研究现状A.卵巢生殖干细胞:

存在性有极大争议;生理意义不明,可能的存在位置:

卵巢皮层（Ovariancortex）卵巢皮层组织下的上皮组织（germinativeepithelium（GE）B.卵巢体细胞干细胞:

thecacell（yes），粒细胞？

C.外源性间充质干细胞:

可以帮助子宫本身的卵泡恢复功能（子宫内膜间充质干细胞;脐带间充质干细胞;骨髓间充质干细胞）,复习重点,