細(xì)胞與細(xì)胞工程.ppt

Cell(JL)phasecontrast.(A)NormalHeLacells;(B)treatedwithstaurosporintoinduceapoptosis;or(C)treatedwiththapsigargintoinduceautophagy(Galluzzietal,2007).(D)Apoptotic,and(E)necroptoticJurkatcells(Degterevetal,2005).(F)Paraptotic293Tcells(Sperandioetal,2000;copyright(2000)NationalAcademyofSciences,USA).(G)Necroticand(H)autophagiciBMKcells(Degenhardtetal,2006;Mathewetal,2007).(I)Ras-expressingU251glioblastomacellsshowingmacropinosomes(J.H.Overmeyer,A.Kaul,E.E.Johnson(3)經(jīng)轉(zhuǎn)基因的克隆哺乳動(dòng)物，將能為人類提供源源不斷的廉價(jià)的藥品、保健品以及較易被人體接受的移植器官；(4)科學(xué)家將很快地從目前的同種克隆技術(shù)推進(jìn)到異種克隆,即借腹懷胎的新領(lǐng)域,這無疑將大大促進(jìn)對(duì)瀕臨滅種的哺乳動(dòng)物的保護(hù)工作。,克隆技術(shù)將對(duì)21世紀(jì)產(chǎn)生的重大影響（？）,第一節(jié)細(xì)胞的特征細(xì)胞的基礎(chǔ)知識(shí)細(xì)胞的生長(zhǎng)、分化與死亡第二節(jié)動(dòng)物細(xì)胞工程動(dòng)物細(xì)胞培養(yǎng)單克隆抗體動(dòng)物克隆干細(xì)胞工程,Stemcellsarepowerfultoolsinbiologyandmedicine.Whatcanscientistsdowiththesecellstoexploittheirincrediblepotential?,AdaptedfromPrinciplesofBiologypublishedbyNatureEducation.,JAMESKING-HOLMES/SCIENCEPHOTOLIBRARYAmouseembryoisheldinplaceduringnucleartransfer.Theeggsgeneticmaterialhasbeenremovedandanadultcellnucleusisinjectedinitsplace.,四.干細(xì)胞工程,Pluripotent:cantransformintoanyoneofthe220celltypesinthehumanbody.Self-renewal:onestemcellcanalsodividetoproducemillionsmorestemcells.,1.WhatareStemCells?,innearlyallanimals,fromtinywormstomiceandhumans.embryonicstemcellsadultstemcellsinducedpluripotentstem(iPS)cells,2.TypesofStemCells,EmbyonicStemCellsVS.AdultStemCells,StemCells:FlexiblefriendsNature483,S22S26,Inthepastdecade,scientistshavealsolearnedtomakestemcellsfromregularmature,differentiatedcells.Thesecellsarecalledinducedpluripotentstemcellsbecausescientistsforcethemtobecomepluripotentevenaftertheyhavereachedadifferentiatedstate.Byturninguptheexpressionofjustafewgenes,scientistscanforceaskincell,forexample,toretraceitsdevelopmentalpathwaybackwardsallthewaytoaflexiblepluripotentstate.,InducedPluripotentStemCells,3.MedicalApplications,Stemcellscanteachusaboutthebiologyofpluripotentcells,howthehumanbodydevelops,andwhathappensduringdisease.Theyarealsoatoolfordevelopingsaferwaystodesignandtestnewmedications.theyarethebasisforregenerativemedicine,usingstemcellstorepairdamagedtissue.,ThediscoveriesofGurdonandYamanakahaveshownthatspecialisedcellscanturnbackthedevelopmentalclockundercertaincircumstances.Althoughtheirgenomeundergoesmodificationsduringdevelopment,thesemodificationsarenotirreversible.Wehaveobtainedanewviewofthedevelopmentofcellsandorganisms.ResearchduringrecentyearshasshownthatiPScellscangiverisetoallthedifferentcelltypesofthebody.Thesediscoverieshavealsoprovidednewtoolsforscientistsaroundtheworldandledtoremarkableprogressinmanyareasofmedicine.iPScellscanalsobepreparedfromhumancells.Forinstance,skincellscanbeobtainedfrompatientswithvariousdiseases,reprogrammed,andexaminedinthelaboratorytodeterminehowtheydifferfromcellsofhealthyindividuals.Suchcellsconstituteinvaluabletoolsforunderstandingdiseasemechanismsandsoprovidenewopportunitiestodevelopmedicaltherapies.,Fromsurprisingdiscoverytomedicaluse,皮膚細(xì)胞,iPS,神經(jīng)細(xì)胞,心肌細(xì)胞,肝細(xì)胞,精子、卵子,Whyisatherapeuticcloningapproachimportant?,Bygrowingnewbodypartsfromexistingonesfromthesamepersonwecanavoidtransplantrejectionproblems.Byusingcellsre-engineeredor“cloned”fromourselveswecanbecomeourowntransplantsource-similartobankingbloodforourselvesbeforeasurgicaloperation.,PeopleintheUSaffectedbydiseasesthatmaybehelpedbystemcellresearch,ConditionNumberofPersonsAffectedCardiovasculardiseases58MillionAutoimmunediseases30MillionDiabetes16MillionOsteoporosis10MillionCancer8.2MillionAlzheimersdisease4MillionParkinsonsdisease1.5MillionBurns(severe)0.3MillionSpinalcordinjuries0.25MillionBirthdefects150,000(peryear)Total128.4Million-DatafromthePatientsCoalitionforUrgentResearch,Washington,DC(accordingtoPerry,Ref.267).,NATURE|NEWSChinasstem-cellrulesgounheededHealthministrysattemptatregulationhashadlittleeffect.Nature484,149150(12April2012),Itsboomtimeforfirmssellingstem-celltreatments,suchasthosederivedfromumbilicalblood.LIUHAIFENG/XINHUAPRESS/CORBIS,NATURE|NEWSStem-celltherapytakesoffinTexasAboominunprovenproceduresisworryingscientists.Nature483,1314(01March2012),Celltexhoststhelargeststem-cellbankintheUnitedStates.TYLERRUDICK,4.DevelopmentoftheStemCelltechnique,Source:,WherearetheStemCells?,自然胚胎克隆人胚胎-核移植/混種胚胎-核移植體細(xì)胞誘導(dǎo)多能干細(xì)胞(體細(xì)胞轉(zhuǎn)分化),In1868,GermanbiologistErnstHaeckelfirstusedthetermstemcelltodescribeazygote.Researchershavebeenworkingwithmouseembryonicstemcellssince1981.thefieldtookoffin1998,whenresearchersisolatedhumanembryonicstemcellsforthefirsttime.（最早的人類多能干細(xì)胞是從體外受精的臨床病例中得來的多余胚泡。這個(gè)里程碑式的事件是JamesThomson領(lǐng)導(dǎo)的UniversityofWisconsin,Madison的實(shí)驗(yàn)室在1998年的成果。）,3.1IsolationandcultureofStemCells,3.2ObjectionstoStemCellReasearch,2008紐卡斯?fàn)柎髮W(xué)將從人類皮膚細(xì)胞中提取的DNA注入來自母牛卵巢的卵子，卵子的所有遺傳物質(zhì)基本上都被去除。,3.3InterspeciesEmbryos,2003上海第二醫(yī)科大學(xué)盛慧珍教授研究組將人的體細(xì)胞核植入去核的兔卵細(xì)胞中。,3.4AdultStemCells,donotraisetheethicalquestionsthatembryonicstemcellsdobecausenoembryosareneededexistinverysmallnumbersoftenburieddeepinthetissuemainlyusedfortwotreatments:bone-marrowtransplantstorebuildapatientsimmunesystem,andskingraftstoreplaceskinoveraburnorotherinjuryotherapplicationsforadultstemcells？usedrugstoactivateapatientsownadultstemcellstoperformthenecessaryrepairs？,Foralongtime,scientiststhoughtthatonceacelldifferentiated,itcouldneverregainitspluripotency.Theyassumedthatitmustbesetinitsidentitybecauseithadsomanygenesturnedonandoffinwaysparticulartothatcelltype.In2006,however,KazutoshiTakahashiandShinyaYamanakaofKyotoUniversityinJapanprovedotherwise.Theyturnedmouseskincellsspecifically,fibroblastsintostemcells.Thesewerethefirstinducedpluripotentstem(iPS)cells.,3.5InducedPluripotentStemCells,Thefirstdirectreprogrammingofadulthumanfibroblasts.IanWilmutScottishCentreforRegenerativeMedicine,UniversityofEdinburghIn2007issuesofCellandScience,Yamanakaandcolleagues(Takahashietal.,2007)andYuandcolleagues(Yuetal.,2007)demonstratethatexpressionoffourspecifictranscriptionfactorsgivesadulthumanfibroblastsmanyofthecharacteristicsofhumanembryonicstemcells.Refinementsofthisprocedurewillmakeitpossibletoproducepluripotenthumancelllineswithoutuseofanembryo.Thereareprofoundscientificandsocialimplicationsofthisresearch.,CellStemCell,2007Dec13;1(6):593-4.,Idecidedafewweeksagonottopursuenucleartransfer-themethodusedtocreateDollythesheep,hesaid,admittingthenewmethodwaseasiertoacceptsocially.,十年科學(xué)進(jìn)展1.TheDarkGenome：基因組中的“暗物質(zhì)”3.AncientDNA：古生物的DNA5.ReprogrammingCells：細(xì)胞重編程6.TheMicrobiome：人體內(nèi)微生物組8.Inflammation：炎癥反應(yīng)的陰暗面,Science,Dec.2010,TheNobelPrizeinPhysiologyorMedicine2012.N.21Feb2013/nobel_prizes/medicine/laureates/2012/,TheNobelPrizerecognizestwoscientistswhodiscoveredthatmature,specialisedcellscanbereprogrammedtobecomeimmaturecellscapableofd