细胞与细胞工程

.,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)经转基因的克隆哺乳动物，将能为人类提供源源不断的廉价的药品、保健品以及较易被人体接受的移植器官；(4)科学家将很快地从目前的同种克隆技术推进到异种克隆,即借腹怀胎的新领域,这无疑将大大促进对濒临灭种的哺乳动物的保护工作。,克隆技术将对21世纪产生的重大影响（？）,.,第一节细胞的特征细胞的基础知识细胞的生长、分化与死亡第二节动物细胞工程动物细胞培养单克隆抗体动物克隆干细胞工程,.,Stemcellsarepowerfultoolsinbiologyandmedicine.Whatcanscientistsdowiththesecellstoexploittheirincrediblepotential?,AdaptedfromPrinciplesofBiologypublishedbyNatureEducation.,JAMESKING-HOLMES/SCIENCEPHOTOLIBRARYAmouseembryoisheldinplaceduringnucleartransfer.Theeggsgeneticmaterialhasbeenremovedandanadultcellnucleusisinjectedinitsplace.,四.干细胞工程,.,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,皮肤细胞,iPS,神经细胞,心肌细胞,肝细胞,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/混种胚胎-核移植体细胞诱导多能干细胞(体细胞转分化),.,In1868,GermanbiologistErnstHaeckelfirstusedthetermstemcelltodescribeazygote.Researchershavebeenworkingwithmouseembryonicstemcellssince1981.thefieldtookoffin1998,whenresearchersisolatedhumanembryonicstemcellsforthefirsttime.（最早的人类多能干细胞是从体外受精的临床病例中得来的多余胚泡。这个里程碑式的事件是JamesThomson领导的UniversityofWisconsin,Madison的实验室在1998年的成果。）,3.1IsolationandcultureofStemCells,.,3.2ObjectionstoStemCellReasearch,.,2008纽卡斯尔大学将从人类皮肤细胞中提取的DNA注入来自母牛卵巢的卵子，卵子的所有遗传物质基本上都被去除。,3.3InterspeciesEmbryos,2003上海第二医科大学盛慧珍教授研究组将人的体细胞核植入去核的兔卵细胞中。,.,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.,.,十年科学进展1.TheDarkGenome：基因组中的“暗物质”3.AncientDNA：古生物的DNA5.ReprogrammingCells：细胞重编程6.TheMicrobiome：人体内微生物组8.Inflammation：炎症反应的阴暗面,Science,Dec.2010,.,TheNobelPrizeinPhysiologyorMedicine2012.N.21Feb2013/nobel_prizes/medicine/laureates/2012/,TheNobelPrizerecognizestwoscientistswhodiscoveredthatmature,specialisedcellscanbereprogrammedtobecomeimmaturecellscapableofde