Generation of Stratified Squamous Epithelial Progenitor Cells from Mouse Induced Pluripotent Stem Cells 英文参考文献.docVIP

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Generation of Stratified Squamous Epithelial Progenitor Cells from Mouse Induced Pluripotent Stem Cells 英文参考文献.doc

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Generation of Stratified Squamous Epithelial Progenitor Cells from Mouse Induced Pluripotent Stem Cells 英文参考文献

GenerationofStratifiedSquamousEpithelialProgenitor CellsfromMouseInducedPluripotentStemCells SatoruYoshida1,MiyukiYasuda1,HideyukiMiyashita1,YokoOgawa1,TetsuYoshida1,YumiMatsuzaki2, KazuoTsubota1,HideyukiOkano2,ShigetoShimmura1* 1DepartmentofOphthalmology,KeioUniversitySchoolofMedicine,Tokyo,Japan,2DepartmentofPhysiology,KeioUniversitySchoolofMedicine,Tokyo,Japan Abstract Background: Application of induced pluripotent stem (iPS) cells in regenerative medicine will bypass ethical issues associated with use of embryonic stem cells. In addition, patient-specific IPS cells can be useful to elucidate the pathophysiology of genetic disorders, drug screening, andtailor-made medicine. However, in order to apply iPS cells to mitotictissue,inductionoftissuestemcellsthatgiverisetoprogenyofthetargetorganisrequired. Methodology/PrincipalFindings:WeinducedstratifiedepithelialcellsfrommouseiPScellsbyco-culturewithPA6feeder cells(SDIA-method)withuseofBMP4.ClustersofcellspositiveforthedifferentiationmarkersKRT1orKRT12wereobserved inKRT14-positivecolonies.WesuccessfullyclonedKRT14andp63double-positivestratifiedepithelialprogenitorcellsfrom iPS-derivedepithelialcells,whichformedstratifiedepithelialsheetsconsistingoffive-tosix-polarizedepithelialcellsinvitro. Whentheseclonalcellswereculturedondenudedmousecorneas,arobuststratifiedepitheliallayerwasobservedwith physiologicalcellpolarityincludinghighlevelsofE-cadherin,p63andK15expressioninthebasallayerandZO-1inthe superficiallayer,recapitulatingtheapico-basalpolarityoftheepitheliuminvivo. Conclusions/Significance: These results suggest that KRT14 and p63 double-positive epithelial progenitor cells can be clonedfromiPScellsinordertoproducepolarizedmultilayerepithelialcellsheets. Citation:YoshidaS,YasudaM,MiyashitaH,OgawaY,YoshidaT,etal.(2011)GenerationofStratifiedSquamousEpithelialProgenitorCellsfromMouseInduced PluripotentStemCells.PLoSONE6(12):e28856.doi:10.1371/journal.pone.0028856 Editor:QiangWu,NationalUniversityofSingapore,Singapor