小鼠胚胎干细胞自我更新的信号调控机制.docx

小鼠胚胎干细胞自我更新的信号调控机制【摘要】小鼠胚胎干细胞是一种全能干细胞，具有体内体外全能分化特性。体外培养时能够进行自我更新，即细胞通过对称分裂在维持全能性不丢失的情况下细胞数目增多。全能性维持受多条信号通路的调控，其中gp130下游的JAK-STAT3及PI3K通路的活化能维持胚胎干细胞的自我更新，而SHP2-Ras-ERK的激活则促使胚胎干细胞分化。无血清条件下BMP4激活的通路与JAK-STAT3联合作用可保持胚胎干细胞的全能性。此外，Wnt信号通路的活化也参与对胚胎干细胞的自我更新的调控。总之，多种信号通路形成的网络精确调控小鼠胚胎干细胞的自我更新与分化。本文主要综述gp130在小鼠ES细胞增殖过程中作用，包括JAK-STAT3通路活化抑制小鼠ES细胞分化，PI3K通路活化维持ES细胞的自我更新和SHP-2-Ras通路活化促进ES细胞分化，以及其他信号通路对小鼠ES细胞自我更新的影响，包括无血清条件下BMP联合LIF能维持ES细胞的高度自我更新，Wnt信号通路活化促进ES细胞自我更新。【关键词】胚胎干细胞自我更新信号通路全能性SignalingPathwaysRegulatingSelf-renewalofMouseEmbryonicStemCells——ReviewAbstractMouseembryonicstemcells(EScells)arepluripotentinthattheycangiverisetoalmostallthecelltypesinvitroandinvivo.Also,theycansustainself-renewalinvitroowingtosymmetricalmitosis,,onlythecellnumberincreaseswhilethedaughtercellsremainpluripotent.Self-renewalandpluripotencyofEScellsareunderstringentregulationofseveralsignalingpathways.ActivationofeitherJAK-STAT3orPI3K,thedownstreamcascadeofgp130,canmaintaintheself-renewalofEScells,whilephosphorylationofanothergp130-relatedbranch,SHP2-Ras-ERK,drivesthedifferentiation.BMP2/4-mediatedsignalingiscapableofsuppressingthedifferentiationofEScellsincollaborationwithactivatedJAK-STAT3underserumfreecultureconditions.OthersignalingsuchasWntalsocontributestotheself-renewalofEScells.Generally,thenetwork,whichiscomposedofvarioussignalingpathways,modulatestheself-renewalanddifferentiationofmouseEScellsprecisely.Thisreviewfocusesontheroleofgp130inproliferationofmouseEScellsincludinginhibitoryeffectofJAK-STAT3pathwayactivationondifferentiationofmouseEScells,maintenanceeffectofPI3Kpathwayactivationonself-renewalofEScells,promotiveeffectofSHP-2-Ras-ERKpathwayactivationondifferentiationofEScells,andinfluenceofothersignalingpathwaysonself-renewalofmouseEScells,includingmaintenanceeffectofBMPcombinationwithLIFunderserumfreecultureconditionsonself-renewalofEScellsandpromotiveeffectofWntpathwayactivationonself-renewalofEScells.Keywordsembryonicstemcell；self-renewal；signalingpathway；pluripotency小鼠胚胎发育过程中的分