Early Cell Fate Decisions of Human Embryonic Stem Cells and Mouse Epiblast Stem Cells Are Controlled by the Same Signalling Pathways 英文参考文献.docVIP

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Early Cell Fate Decisions of Human Embryonic Stem Cells and Mouse Epiblast Stem Cells Are Controlled by the Same Signalling Pathways 英文参考文献.doc

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Early Cell Fate Decisions of Human Embryonic Stem Cells and Mouse Epiblast Stem Cells Are Controlled by the Same Signalling Pathways 英文参考文献

EarlyCellFateDecisionsofHumanEmbryonicStemCells andMouseEpiblastStemCellsAreControlledbythe SameSignallingPathways LudovicVallier1*,ThomasTouboul1,2,ZhenzhiChng1,MinodoraBrimpari1,NicholasHannan1 ,Enrique Millan1¤a,LucyE.Smithers3¤b,MatthewTrotter1,PeterRugg-Gunn4,AnneWeber2,RogerA.Pedersen1 1DepartmentofSurgeryandLaboratoryforRegenerativeMedicine,UniversityofCambridge,Cambridge,UnitedKingdom,2Laboratoiredetransfertdege`nes dansle foie:applicationsthe′rapeutiques, EquipeMixteInsermU804,Universite′ ParisXIBa?timent GregoryPincus,LeKremlinBice?tre,France,3WolfsonInstituteforBiomedical Research,UniversityCollegeLondon,London,UnitedKingdom,4HospitalforSickChildren,TorontoMedicalDiscoveryTower,Toronto,Ontario,Canada Abstract Human embryonic stem cells have unique value for regenerative medicine, as they are capable of differentiating into a broadvarietyofcelltypes.Therefore,definingthesignallingpathwaysthatcontrolearlycellfatedecisionsofpluripotent stemcellsrepresentsamajortask.Moreover,modellingtheearlystepsofembryonicdevelopmentinvitromayprovidethe bestapproachtoproducecelltypeswithnativeproperties.Here,weanalysedthefunctionofkeydevelopmentalgrowth factorssuchasActivin,FGFandBMPinthecontrolofearlycellfatedecisionsofhumanpluripotentstemcells.Thisanalysis resultedinthedevelopmentandvalidationofchemicallydefinedcultureconditionsforachievingspecificationofhuman embryonic stem cells into neuroectoderm, mesendoderm and into extra-embryonic tissues. Importantly, these defined cultureconditionsaredevoidoffactorsthatcouldobscureanalysisofdevelopmentalmechanismsorrendertheresulting tissues incompatible with future clinical applications. Importantly, the growth factor roles defined using these culture conditions similarly drove differentiation of mouse epiblast stem cells derived from post implantation embryos, thereby reinforcingthehypothesisthatepiblaststemcellsshareacommonembryonicidentitywithhumanpluripotentstemcells. Thereforethedefinedgrowthfactorconditionsde