2016
EGLN1 Inhibition and Rerouting of α-Ketoglutarate Suffice for Remote Ischemic Protection
Olenchock B, Moslehi J, Baik A, Davidson S, Williams J, Gibson W, Chakraborty A, Pierce K, Miller C, Hanse E, Kelekar A, Sullivan L, Wagers A, Clish C, Vander Heiden M, Kaelin W. EGLN1 Inhibition and Rerouting of α-Ketoglutarate Suffice for Remote Ischemic Protection. Cell 2016, 164: 884-895. PMID: 26919427, PMCID: PMC4819986, DOI: 10.1016/j.cell.2016.02.006.Peer-Reviewed Original ResearchConceptsRemote ischemic preconditioningIschemic preconditioningHypoxia-inducible factorKynurenic acidIschemic protectionMyocardial ischemia-reperfusion (I/R) injuryIschemia-reperfusion (I/R) injuryParabiosis experimentsPeriod of sublethal ischemiaMouse modelIschemic insultSecreted factorsPharmacological inhibitorsHepatic productionOther organsGene deletionSublethal ischemiaIschemiaMiceEGLN1Inhibition
2015
Young, Proliferative Thymic Epithelial Cells Engraft and Function in Aging Thymuses
Kim M, Miller C, Shadrach J, Wagers A, Serwold T. Young, Proliferative Thymic Epithelial Cells Engraft and Function in Aging Thymuses. The Journal Of Immunology 2015, 194: 4784-4795. PMID: 25870244, PMCID: PMC4481326, DOI: 10.4049/jimmunol.1403158.Peer-Reviewed Original ResearchConceptsThymic epithelial cellsAge-related thymic involutionMolecular processesColony-forming assayAged thymusCell-intrinsic changesThymic growthProliferative capacityEpithelial cellsIn vitro colony-forming assayIncreased T cell productionT-cell recoveryT-cell lymphopeniaBone marrow transplantationT cell productionAntigen- and Cytokine-Driven Accumulation of Regulatory T Cells in Visceral Adipose Tissue of Lean Mice
Kolodin D, van Panhuys N, Li C, Magnuson A, Cipolletta D, Miller C, Wagers A, Germain R, Benoist C, Mathis D. Antigen- and Cytokine-Driven Accumulation of Regulatory T Cells in Visceral Adipose Tissue of Lean Mice. Cell Metabolism 2015, 21: 543-557. PMID: 25863247, PMCID: PMC4747251, DOI: 10.1016/j.cmet.2015.03.005.Peer-Reviewed Original ResearchConceptsVisceral adipose tissueTreg compartmentT cellsAccumulation of regulatory T cellsConventional CD4(+) T cellsCD4(+) T cellsRegulatory T cellsAdipose tissueMHC class II moleculesEpidemic of obesityClass II moleculesAntigen receptor repertoireWeeks of lifeConsequent metabolic abnormalitiesIndolent proliferationsVAT-TregRegulatory TLean miceMetabolic abnormalitiesLocal inflammationLymphoid organsSoluble mediatorsLean individualsMetabolic indicesPhenotypic conversion
2014
Diminished Schwann Cell Repair Responses Underlie Age-Associated Impaired Axonal Regeneration
Painter M, Lutz A, Cheng Y, Latremoliere A, Duong K, Miller C, Posada S, Cobos E, Zhang A, Wagers A, Havton L, Barres B, Omura T, Woolf C. Diminished Schwann Cell Repair Responses Underlie Age-Associated Impaired Axonal Regeneration. Neuron 2014, 83: 331-343. PMID: 25033179, PMCID: PMC4106408, DOI: 10.1016/j.neuron.2014.06.016.Peer-Reviewed Original ResearchConceptsImpairment of functional recoverySchwann cellsSensory neurons in vitroFunctional recoveryMyelin clearanceNeurons in vitroIntrinsic growth capacityTransplantation in vivoPeripheral nervous systemSchwann cell plasticityNerve injuryMacrophage recruitmentAge-associated declineNerve graftsSciatic nerveCell plasticityRegenerative capacityAxonal regenerationNervous systemMolecular interrogationNerveTranscriptional programsInjuryAgeClearanceRestoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle
Sinha M, Jang Y, Oh J, Khong D, Wu E, Manohar R, Miller C, Regalado S, Loffredo F, Pancoast J, Hirshman M, Lebowitz J, Shadrach J, Cerletti M, Kim M, Serwold T, Goodyear L, Rosner B, Lee R, Wagers A. Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle. Science 2014, 344: 649-652. PMID: 24797481, PMCID: PMC4104429, DOI: 10.1126/science.1251152.Peer-Reviewed Original ResearchConceptsGDF11 levelsSystemic delivery of recombinant proteinsAged miceSkeletal muscleStem cell dysfunctionAged muscle stem cellsDelivery of recombinant proteinsMuscle stem cellsGrowth differentiation factor 11Differentiation factor 11Parabiosis experimentsSystemic deliveryMouse skeletal muscleImpaired regenerationSatellite cellsCell dysfunctionExercise capacityHeterochronic parabiosisYoung bloodStem cellsFactor 11Regenerative functionMiceMuscle agingRejuvenation factorVascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors
Katsimpardi L, Litterman N, Schein P, Miller C, Loffredo F, Wojtkiewicz G, Chen J, Lee R, Wagers A, Rubin L. Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors. Science 2014, 344: 630-634. PMID: 24797482, PMCID: PMC4123747, DOI: 10.1126/science.1251141.Peer-Reviewed Original ResearchConceptsAssociated with reduced blood flowImproved olfactory discriminationAdult central nervous systemDecline of neurogenesisAged mouse brainAge-related declineCentral nervous systemNegative effects of agingNeural stem cellsOlfactory discriminationAge-related decline of neurogenesisCognitive functionAged miceIncreased neurogenesisNeural stem cell behaviorVascular remodelingSecreted factorsEffects of ageEnhanced neurogenesisYoung bloodStem cellsStem cell behaviorBlood flowNeurogenic nicheNervous system
2013
Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy
Loffredo F, Steinhauser M, Jay S, Gannon J, Pancoast J, Yalamanchi P, Sinha M, Dall’Osso C, Khong D, Shadrach J, Miller C, Singer B, Stewart A, Psychogios N, Gerszten R, Hartigan A, Kim M, Serwold T, Wagers A, Lee R. Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy. Cell 2013, 153: 828-839. PMID: 23663781, PMCID: PMC3677132, DOI: 10.1016/j.cell.2013.04.015.Peer-Reviewed Original ResearchConceptsCardiac hypertrophyYoung miceOld miceCirculating factorsTreatment of old miceAge-related hypertrophyReduced cardiomyocyte sizeGrowth differentiation factor 11Aptamer-based proteomicsDifferentiation factor 11Blood-borne factorsReverse age-related cardiac hypertrophyCardiomyocyte sizeHeart failureSurgical techniqueHypertrophyCardiac agingHeterochronic parabiosisTherapeutic opportunitiesTGF-bFactor 11Influence of circulation factorsBehavioral effectsMiceMolecular remodeling
2012
Induction of Histiocytic Sarcoma in Mouse Skeletal Muscle
Liu J, Hettmer S, Milsom M, Hofmann I, Hua F, Miller C, Bronson R, Wagers A. Induction of Histiocytic Sarcoma in Mouse Skeletal Muscle. PLOS ONE 2012, 7: e44044. PMID: 22952867, PMCID: PMC3432091, DOI: 10.1371/journal.pone.0044044.Peer-Reviewed Original ResearchConceptsMyeloid sarcomaAcute myeloid leukemiaBone marrowHistiocytic sarcomaAccumulation of immature myeloid cellsDiagnosis of acute myeloid leukemiaEvidence of pathologic involvementEx vivo transductionImmature myeloid cellsLeukemia-initiating cellsNon-hematopoietic organsBone marrow cellsHematopoietic lineage markersSarcoma-bearing miceTumor-bearing animalsSkeletal muscleInduce tumor formationImmunocompromised NODSecondary transplantationMyeloid leukemiaPeripheral bloodMarrow cellsMyeloid cellsAbsent expressionIntravenous transplantation
2011
Sarcomas induced in discrete subsets of prospectively isolated skeletal muscle cells
Hettmer S, Liu J, Miller C, Lindsay M, Sparks C, Guertin D, Bronson R, Langenau D, Wagers A. Sarcomas induced in discrete subsets of prospectively isolated skeletal muscle cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 20002-20007. PMID: 22135462, PMCID: PMC3250188, DOI: 10.1073/pnas.1111733108.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorCell LineageCell ProliferationCell SeparationCell Transformation, NeoplasticGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunohistochemistryMiceMice, Inbred C57BLMuscle CellsMuscle DevelopmentMuscle Fibers, SkeletalMuscle NeoplasmsMuscle, SkeletalRas ProteinsRatsSarcomaSignal TransductionTOR Serine-Threonine KinasesTranscriptomeConceptsMechanistic target of rapamycinRhabdomyosarcoma cells in vitroHuman rhabdomyosarcomaTumor cell of originKirsten rat sarcoma viral oncogeneCyclin-dependent kinase inhibitor 2AIsolated skeletal muscle cellsRat sarcoma viral oncogeneChimeric mouse modelSoft tissue sarcomasIsolated satellite cellsCell of originMechanistic target of rapamycin signalingCells in vitroGene expression signaturesMesenchymal cell lineagesConsistent with activationSkeletal muscle cellsMyogenic featuresTissue-specific differentiation markersPleomorphic rhabdomyosarcomaCluster of genesInhibition of RasTarget of rapamycinHeterogeneous cancer