Differential Genomic Imprinting and Expression of Imprinted microRNAs in Testes-Derived Male Germ-Line Stem Cells in Mouse 英文参考文献.docVIP

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Differential Genomic Imprinting and Expression of Imprinted microRNAs in Testes-Derived Male Germ-Line Stem Cells in Mouse 英文参考文献.doc

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Differential Genomic Imprinting and Expression of Imprinted microRNAs in Testes-Derived Male Germ-Line Stem Cells in Mouse 英文参考文献

DifferentialGenomicImprintingandExpressionof ImprintedmicroRNAsinTestes-DerivedMaleGerm-Line StemCellsinMouse JiYoungShin,MukeshKumarGupta*,YoonHeeJung,SangJunUhm,HoonTaekLee* Department of Animal Biotechnology, Bio-Organ Research Center/Animal Resources Research Center, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul, South Korea Abstract Background:Testis-derivedmalegerm-linestem(GS)cells,theinvitrocounterpartofspermatogonialstemcells(SSC),can acquire multipotency under appropriate culture conditions to become multipotent adult germ-line stem (maGS) cells, whichupontesticulartransplantation,produceteratomainsteadofinitiatingspermatogenesis.Consequently,amolecular markerthatcandistinguishGScellsfrommaGScellswouldbeofpotentialvalueinbothclinicalandexperimentalresearch settings. MethodsandFindings:Usingmouseasamodelsystem,hereweshowthat,similartosperm,expressionofimprintedand paternally expressed miRNAs (miR-296-3p, miR-296-5p, miR-483) were consistently higher (P,0.001), while those of imprinted and maternally expressed miRNA (miR-127, miR-127-5p) were consistently lower (P,0.001) in GS cells than in controlembryonicstem(ES)cells.DNAmethylationanalysesofimprintingcontrolregions(ICR),thatcontroltheexpression ofallimprintedmiRNAsinrespectivegeneclusters(Gnas-NespasDMR,Igf2-H19ICRandDlk1-Dio3IG-DMR),confirmedthat imprintedmiRNAswereandrogeneticinGScells.Ontheotherhand,DNAmethylationofimprintedmiRNAgenesinmaGS cellsresembledthoseofEScellsbuttheexpressionpatternoftheimprintedmiRNAswasintermediatebetweenthoseofGS andEScells.TheexpressionofimprintedmiRNAsinGSandmaGScellswerealsoalteredduringtheirinvitrodifferentiation andvariedbothwiththedifferentiationstageandthemiRNA. Conclusions: Our data suggest that GS cells have androgenetic DNA methylation and expression of imprinted miRNAs which changes to ES cell-like pattern upon their conversion to maGS cells. Differential genomic imprinting of imprinted miRNAsmaythus,serveasepigeneticmiRNAsignatureormolecularmarkertodisti