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Pdx-1 and Ptf1a concurrently determine fate specification of pancreatic multipotent progenitor cells

机译:Pdx-1和Ptf1a同时确定胰腺多能祖细胞的命运规格

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Thepancreasisderivedfromapoolofmultipotentprogenitorcells(MPCs)thatco-expressemPdx-1/emandemPtf1a/em.TomorepreciselydefinehowtheindividualandcombinedlossofemPdx-1/emandemPtf1a/emaffectspancreaticMPCspecificationanddifferentiationwederivedandstudiedmicebearinganovelemPtf1a/emsupemYFP/em/supallele.WhiletheexpressionofemPdx-1/emandemPtf1a/eminpancreaticMPCscoincidesbetweenE9.5and12.5thedevelopmentalphenotypesofPdx-1nullandPdx-1;Ptf1adoublenullmiceareindistinguishable,andanearlypancreaticbudisformedinbothcases.ThisfindingindicatesthatPdx-1isrequiredintheforegutendodermpriortoPtf1aforpancreaticMPCspecification.WealsofoundthatemPtf1a/emisneitherrequiredforspecificationofNgn3-positiveendocrineprogenitorsnordifferentiationofmatureβ-cells.IntheabsenceofemPdx-1/emNgn3-positivecellswerenotobservedafterE9.5.Thus,incontrasttothedeletionofemPtf1a/em,thelossofemPdx-1/emprecludesthesustainedNgn3-basedderivationofendocrineprogenitorsfrompancreaticMPCs.Takentogether,thesestudiesindicatethatPdx-1andPtf1ahavedistinctbutinterdependentfunctionsduringpancreaticMPCspecification./p/div
机译:胰腺源于共同表达 Pdx-1 Ptf1a 的多能祖细胞(MPC)。准确地定义了 Pdx-1 Ptfa的个体和联合损失> Ptf1a YFP 等位基因1; Ptf1adoublenullmiceareindistinguishable,andanearlypancreaticbudisformedinbothcases.ThisfindingindicatesthatPdx-1isrequiredintheforegutendodermpriortoPtf1aforpancreaticMPCspecification.Wealsofoundthat <位置> PTF1A 的isneitherrequiredforspecificationofNgn3-positiveendocrineprogenitorsnordifferentiationofmatureβ-cells.Intheabsenceof <位置> PDX-1 的Ngn3的-positivecellswerenotobservedafterE9.5.Thus,incontrasttothedeletionof <位置> PTF1A Pdx-1 的损失排除了胰腺MPC持续内源性Ngn3衍生的内分泌祖细胞在一起,这些研究表明,在胰腺MPC规范化过程中,Pdx-1和Ptf1具有不同但相互依赖的功能。

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