MicroRNA Biogenesis Is Required for Mouse Primordial Germ Cell Development and Spermatogenesis 英文参考文献.docVIP

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MicroRNA Biogenesis Is Required for Mouse Primordial Germ Cell Development and Spermatogenesis 英文参考文献.doc

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MicroRNA Biogenesis Is Required for Mouse Primordial Germ Cell Development and Spermatogenesis 英文参考文献

MicroRNABiogenesisIsRequiredforMousePrimordial GermCellDevelopmentandSpermatogenesis KatsuhikoHayashi1,SusanaM.ChuvadeSousaLopes1,MasahiroKaneda1,FuchouTang1 ,Petra Hajkova1,KaiqinLao2,DonalO’Carroll3,ParthaP.Das1,AlexanderTarakhovsky3,EricA.Miska1,M.Azim Surani1* 1WellcomeTrust/CancerResearchUnitedKingdomGurdonInstitute,UniversityofCambridge,Cambridge,UnitedKingdom,2AdvancedResearchTechnology,Applied Biosystems, Foster City, California, United States of America, 3Laboratory of Lymphocyte Signaling, The Rockefeller University, New York, New York, United States of America Abstract Background:MicroRNAs(miRNAs)arecriticalregulatorsoftranscriptionalandpost-transcriptionalgenesilencing,whichare involvedinmultipledevelopmentalprocessesinmanyorganisms.ApartfrommiRNAs,mousegermcellsexpressanother type of small RNA, piwi-interacting RNAs (piRNAs). Although it has been clear that piRNAs play a role in repression of retrotransposonsduringspermatogenesis,thefunctionofmiRNAinmousegermcellshasbeenunclear. Methodology/PrincipalFindings:Inthisstudy,wefirstrevealedtheexpressionpatternofmiRNAsbyusingareal-timePCR- based220-plexmiRNAexpressionprofilingmethod.Duringdevelopmentofgermcells,miR-17-92cluster,whichisthought to promote cell cycling, and the ES cell-specific cluster encoding miR-290 to -295 (miR-290-295 cluster) were highly expressedinprimordialgermcells(PGCs)andspermatogonia.AsetofmiRNAswasdevelopmentallyregulated.Wenext analysedfunctionofmiRNAbiogenesisingermcelldevelopmentbyusingconditionalDicer-knockoutmiceinwhichDicer gene was deleted specifically in the germ cells. Dicer-deleted PGCs and spermatogonia exhibited poor proliferation. Retrotransposon activity was unexpectedly suppressed in Dicer-deleted PGCs, but not affected in the spermatogonia. In Dicer-deleted testis, spermatogenesis was retarded at an early stage when proliferation and/or early differentiation. Additionally, we analysed spermatogenesis in conditional Argonaute2-deficient mice. In contrast to Dicer-de