A Conserved Mechanism for Control of Human and Mouse Embryonic Stem Cell Pluripotency and Differentiation by Shp2 Tyrosine Phosphatase 英文参考文献.docVIP

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A Conserved Mechanism for Control of Human and Mouse Embryonic Stem Cell Pluripotency and Differentiation by Shp2 Tyrosine Phosphatase 英文参考文献.doc

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A Conserved Mechanism for Control of Human and Mouse Embryonic Stem Cell Pluripotency and Differentiation by Shp2 Tyrosine Phosphatase 英文参考文献

AConservedMechanismforControlofHumanand MouseEmbryonicStemCellPluripotencyand DifferentiationbyShp2TyrosinePhosphatase DongmeiWu1.,YuhongPang1.,YuehaiKe1,JianxiuYu1,ZhaoHe1,LutzTautz1,TomasMustelin1, ShengDing2,ZiweiHuang1,Gen-ShengFeng1* 1ProgramsinSignalTransduction,andStemCellsandRegeneration,BurnhamInstituteforMedicalResearch,LaJolla,California,UnitedStatesofAmerica,2Department ofChemistry,ScrippsResearchInstitute,LaJolla,California,UnitedStatesofAmerican Abstract Recent studies have suggested distinctive biological properties and signaling mechanisms between human and mouse embryonic stem cells (hESCs and mESCs). Herein we report that Shp2, a protein tyrosine phosphatase with two SH2 domains,hasaconservedroleinorchestrationofintracellularsignalingcascadesresultingininitiationofdifferentiationin both hESCs and mESCs. Homozygous deletion of Shp2 in mESCs inhibited differentiation into all three germ layers, and siRNA-mediated knockdown of Shp2 expression in hESCs led to a similar phenotype of impaired differentiation. A small moleculeinhibitorofShp2enzymesuppressedbothhESCandmESCdifferentiationcapacity.Shp2modulatesErk,Stat3and Smad pathways in ES cells and, in particular, Shp2 regulates BMP4-Smad pathway bi-directionally in mESCs and hESCs. TheseresultsrevealacommonsignalingmechanismsharedbyhumanandmouseESCsviaShp2modulationofoverlapping anddivergentpathways. Citation: Wu D, Pang Y, Ke Y, Yu J, He Z, et al. (2009) A Conserved Mechanism for Control of Human and Mouse Embryonic Stem Cell Pluripotency and DifferentiationbyShp2TyrosinePhosphatase.PLoSONE4(3):e4914.doi:10.1371/journal.pone.0004914 Editor:MaurizioCapogrossi,IstitutoDermopaticodell’Immacolata,Italy ReceivedOctober1,2008;AcceptedFebruary10,2009;PublishedMarch17,2009 Copyright:?2009Wuetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:This