Ptk7 Marks the First Human Developmental EMT In Vitro 英文参考文献.docVIP

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Ptk7 Marks the First Human Developmental EMT In Vitro 英文参考文献.doc

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Ptk7 Marks the First Human Developmental EMT In Vitro 英文参考文献

Ptk7MarkstheFirstHumanDevelopmentalEMTInVitro DavidN.Chan1,2,SoheilaF.Azghadi1,2,JunFeng5,WilliamE.Lowry1,2,3,4* 1DepartmentofMolecularCellandDevelopmentalBiology,UniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesofAmerica,2EliandEdytheBroad Center for Regenerative Medicine, University of California Los Angeles, Los Angeles, California, United States of America, 3Jonsson Comprehensive Cancer Center, University ofCalifornia Los Angeles,Los Angeles,California, United States ofAmerica, 4Molecular Biology Institute, University ofCaliforniaLos Angeles, Los Angeles, California,UnitedStatesofAmerica,5DepartmentofMedicalandMolecularPharmacology,UniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesof America Abstract Epithelialtomesenchymaltransitions(EMTs)arethoughttobeessentialtogeneratediversityoftissuesduringearlyfetal development,buttheseeventsareessentiallyimpossibletostudyatthemolecularlevelinvivoinhumans.ThefirstEMT event that has been described morphologically in human development occurs just prior to generation of the primitive streak. Because human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) are thought to most closelyresemblecellsfoundinepiblast-stageembryospriortoformationoftheprimitivestreak,wesoughttodetermine whetherthisfirsthumanEMTcouldbemodeledinvitrowithpluripotentstemcells.Thedatapresentedheresuggestthat generatingembryoidbodiesfromhESCsorhiPSCsdrivesaprocessionofEMTeventsthatcanbeobservedwithin24–48 hoursafterEBgeneration.ThesestructurespossessthetypicalhallmarksofdevelopmentalEMTs,andportionsalsodisplay evidenceofprimitivestreakandmesendoderm.WeidentifyPTK7asanovelmarkerofthisEMTpopulation,whichcanalso be used to purify these cells for subsequent analyses and identification of novel markers of human development. Gene expressionanalysisindicatedanupregulationofEMTmarkersandECMproteinsinthePTK7+population.Wealsofindthat cells that undergo this developmental EMT retain developmental plasticity