Molecular Phenotyping of Immune Cells from Young NOD Mice Reveals Abnormal Metabolic Pathways in the Early Induction Phase of Autoimmune Diabetes 英文参考文献.docVIP

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Molecular Phenotyping of Immune Cells from Young NOD Mice Reveals Abnormal Metabolic Pathways in the Early Induction Phase of Autoimmune Diabetes 英文参考文献.doc

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Molecular Phenotyping of Immune Cells from Young NOD Mice Reveals Abnormal Metabolic Pathways in the Early Induction Phase of Autoimmune Diabetes 英文参考文献

MolecularPhenotypingofImmuneCellsfromYoung NODMiceRevealsAbnormalMetabolicPathwaysinthe EarlyInductionPhaseofAutoimmuneDiabetes JianWu1,2,4,DorothyN.Kakoola1,2,NataliyaI.Lenchik1,2,DominicM.Desiderio1,3,DanaR.Marshall2,5 IvanC.Gerling1,2 , * 1DepartmentofMedicine,UniversityofTennesseeHealthScienceCenter,Memphis,Tennessee,UnitedStatesofAmerica,2ResearchService,VeteransAffairsMedical Center, Memphis, Tennessee, United States of America, 3Department of Neurology, Department of Molecular Science, and the Charles B. Stout Neuroscience Mass SpectrometryLaboratory,UniversityofTennesseeHealthScienceCenter,Memphis,Tennessee,UnitedStatesofAmerica,4DepartmentofNeurology,XuanWuHospital, Capital Medical University, Beijing, China, 5Department of Pathology, Anatomy and Cell Biology, School of Medicine, Meharry Medical College, Nashville, Tennessee, UnitedStatesofAmerica Abstract Isletleukocyticinfiltration(insulitis)isfirstobviousataround4weeksofageintheNODmouse–amodelforhumantype1 diabetes(T1D).Themoleculareventsthatleadtoinsulitisandinitiateautoimmunediabetesarepoorlyunderstood.Since TIDiscausedbynumerousgenes,wehypothesizedthatmultiplemolecularpathwaysarealteredandinteracttoinitiatethis disease. We evaluated the molecular phenotype (mRNA and protein expression) and molecular networks of ex vivo unfractionatedspleenleukocytesfrom2and4week-oldNODmiceincomparisontotwocontrolstrains.Analysisofthe globalgeneexpressionprofilesandhierarchicalclusteringrevealedthatthemajority(,90%)ofthedifferentiallyexpressed genes in NOD mice were repressed. Furthermore, analysis using a modern suite of multiple bioinformatics approaches identified abnormalmolecular pathwaysthat canbedividedbroadly into2 categories:metabolic pathways,which were predominant at 2 weeks, and immune response pathways, which were predominant at 4 weeks. Network analysis by Ingenuity pathway analysis identified key genes/molecules that may play a role in regulating these pathways. These includedfivethatwerecommontoboth