诱导细胞功能转化的新策略_谱系重编程

小专论*王璞汤奇胜陈露萍沈亦雯沙红英朱剑虹!(,200032;,,,200040)通过重编程诱导细胞功能转化是当前再生医学研究领域的热点其中一种策略是,先将普通成体细胞转变为多能干细胞,再诱导后者向新的细胞类型分化近来新出现的另一种策略是,直接将成熟细胞转分化为其他类型的功能细胞或祖细胞,此即谱系重编程(lineagereprogramming)本文主要就谱系重编程概念的由来相关研究进展及下一步研究方向等内容做一综述谱系重编程;转分化;胰岛细胞;再生医学Q813.5,,[1],∀#2008,DouglasMelton,[2]2010127,MariusWernig,(inducedpluripotentstemcells,iPS),[3],,Waddington:(epigeneticlandscape),,,,[4](1A),,∀#(1B)Weissman(2001),,,,,,DNA2006,Yamanaka24,Oct3/4Sox2cMycKLF4(embryonicstemcel,lESCs)iPS[5]2007,iPS,∀#,iPS∀#,,()iPS,1973,EguchiOkada(transdifferentiation),*(973)(2010CB945500,2007CB947902,2009CB941100),(30870805,90919002),(08dj1400503,075407070)!3592010415(1C)2002,BrockesKumar,,,,2008,Orkin[6]1A.,;B.,,;C./,1990,Choi(myogenicdifferentiationantigen,MyoD)2004,XieCCAAT(C/EBP)B,2005,Raphael,Math1,,,,,∀#,,2003,,Pdx1NeuroD1(Betacellulin(BTC)),,,,2008,Zhou,9,GFP,,Ngn3Pdx1Mafa20%(2),[2],Zhou,,,,∀#2ZhouA.;B.,,,;C.,,,20093,Speer[7],Gla(MGP/)(smoothmusclecells,SMCs),2010,Vierbuchen19,,32,;3(Ascl1,Brn2Myt1l),,20%,,3602010415[3],,:???,,,∀(lockin)#,,,,,20073,science[8],p75NTR,20088,DanaFarber[9],PRDM16,,,,,,20093,celliPS,,[10],,,,,,,,,,,GeorgeDaleyMariusWernig,∀,Yamanaka#1BlellochR.Regenerativemedicine:shortcuttocellreplacement.Nature,2008,455604~605.2ZhouQ,BrownJ,KanarekA,eta.lInvivoreprogrammingofadultpancreaticexocrinecellstocells.Nature,2008,455627~632.3VierbuchenT,OstermeierA,PangZP,eta.lDirectconversionoffibroblaststofunctionalneuronsbydefinedfactors.Nature,2010,4631035~1041.4WaddingtonCH.Thestrategyofthegenes.London:GeoAllenandUnwin,1957.5TakahashiK,YamanakaS.Inductionofpluripotentstemcellsfrommouseembryonicandadultfibroblastculturesbydefinedfactors.Cel,l2006,126663~676.6OrkinSH,ZonLI.Hematopoiesis:anevolvingparadigmforstemcellbiology.Cel,l2008,132631~644.7SpeerMY,YangHY,BrabbT,eta.lSmoothmusclecellsgiverisetoosteochondrogenicprecursorsandchondrocytesincalcifyingarteries.CircRes,2009,104733~741.8PassinoMA,AdamsRA,SikorskiSL,eta.lRegulationofhepaticstellatecelldifferentiationbytheneurotrophinreceptorp75NTR.Science,2007,3151853~1856.9SealeP,BjorkB,YangW,eta.lPRDM16controlsabrownfat/skeletalmuscleswitch.Nature,2008,454961~967.10SoldnerF,HockemeyerD,BeardC,eta.lParkinson'sdiseasepatientderivedinducedpluripotentstemcellsfreeofviralreprogrammingfactors.Cel,l2009,136964~977.3612010415