2023
Apoptosis recognition receptors regulate skin tissue repair in mice
Justynski O, Bridges K, Krause W, Forni M, Phan Q, Sandoval-Schaefer T, Carter K, King D, Hsia H, Gazes M, Vyce S, Driskell R, Miller-Jensen K, Horsley V. Apoptosis recognition receptors regulate skin tissue repair in mice. ELife 2023, 12: e86269. PMID: 38127424, PMCID: PMC10735221, DOI: 10.7554/elife.86269.Peer-Reviewed Original ResearchIL-6 trans-signaling in a humanized mouse model of scleroderma
Odell I, Agrawal K, Sefik E, Odell A, Caves E, Kirkiles-Smith N, Horsley V, Hinchcliff M, Pober J, Kluger Y, Flavell R. IL-6 trans-signaling in a humanized mouse model of scleroderma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2306965120. PMID: 37669366, PMCID: PMC10500188, DOI: 10.1073/pnas.2306965120.Peer-Reviewed Original ResearchConceptsBone marrow-derived immune cellsIL-6Human hematopoietic stem cellsImmune cellsT cellsScleroderma skinSoluble IL-6 receptorCD8 T cellsHumanized mouse modelPathogenesis of sclerodermaMesenchymal cellsFibroblast-derived IL-6IL-6 receptorIL-6 signalingT cell activationHuman IL-6Human T cellsExpression of collagenFibrosis improvementPansclerotic morpheaHuman endothelial cellsHumanized miceReduced markersSkin graftsHuman CD4
2022
Langerhans cells are essential components of the angiogenic niche during murine skin repair
Wasko R, Bridges K, Pannone R, Sidhu I, Xing Y, Naik S, Miller-Jensen K, Horsley V. Langerhans cells are essential components of the angiogenic niche during murine skin repair. Developmental Cell 2022, 57: 2699-2713.e5. PMID: 36493773, PMCID: PMC10848275, DOI: 10.1016/j.devcel.2022.11.012.Peer-Reviewed Original ResearchConceptsAngiogenic nicheSingle-cell RNA sequencingLangerhans cellsControl of angiogenesisCanonical roleMouse geneticsPre-existing vesselsRNA sequencingImmune cellsSkin repairFunction of LCSkin-resident immune cellsNew blood vesselsMouse skin woundsThree-dimensional microscopyNicheNon-healing woundsEndothelial cellsAngiogenesisCellsCell immunityTreatment optionsInflammatory diseasesAntigen presentationInjury repairReindeer light the way to scarless wound healing
Caves E, Horsley V. Reindeer light the way to scarless wound healing. Cell 2022, 185: 4675-4677. PMID: 36493748, DOI: 10.1016/j.cell.2022.11.013.Peer-Reviewed Original ResearchDynamic quality control machinery that operates across compartmental borders mediates the degradation of mammalian nuclear membrane proteins
Tsai P, Cameron C, Forni M, Wasko R, Naughton B, Horsley V, Gerstein M, Schlieker C. Dynamic quality control machinery that operates across compartmental borders mediates the degradation of mammalian nuclear membrane proteins. Cell Reports 2022, 41: 111675. PMID: 36417855, PMCID: PMC9827541, DOI: 10.1016/j.celrep.2022.111675.Peer-Reviewed Original ResearchConceptsProtein turnoverCellular quality control systemNuclear membrane proteinsQuality control machineryDistinct cellular compartmentsNuclear envelope proteinsGenetic screenProtein homeostasisUbiquitin ligasesControl machineryMembrane proteinsCellular compartmentsEnzyme Ube2g2Quality control systemEndoplasmic reticulumHuman diseasesEfficient biosynthesisHRD1RNF5Disease variantsTMEM33Envelope proteinSubstrate levelsDisease etiologyModel substrateAdipocyte plasticity in tissue regeneration, repair, and disease
Horsley V. Adipocyte plasticity in tissue regeneration, repair, and disease. Current Opinion In Genetics & Development 2022, 76: 101968. PMID: 35988318, DOI: 10.1016/j.gde.2022.101968.Peer-Reviewed Original ResearchConceptsMammalian tissue repairTissue repairEssential regulatorAdipocyte plasticityFunction of adipocytesCritical regulatorLipid-filled cellsMultiple tissuesTissue functionRegenerative medicineAdipocytesSkeletal muscleBioactive productsRegulatorMammary glandTherapeutic avenuesFibrotic lesionsEndocrine functionTissue regenerationPlasticityWound healingContractile fibroblastsTissueRepairTumorigenesis
2021
Skin Fibrosis and Recovery Is Dependent on Wnt Activation via DPP4
Jussila AR, Zhang B, Caves E, Kirti S, Steele M, Hamburg-Shields E, Lydon J, Ying Y, Lafyatis R, Rajagopalan S, Horsley V, Atit RP. Skin Fibrosis and Recovery Is Dependent on Wnt Activation via DPP4. Journal Of Investigative Dermatology 2021, 142: 1597-1606.e9. PMID: 34808238, PMCID: PMC9120259, DOI: 10.1016/j.jid.2021.10.025.Peer-Reviewed Original ResearchConceptsWnt/β-catenin-responsive geneWnt activationExtracellular matrix homeostasisGenetic evidenceHuman fibrotic diseasesLipid-filled cellsFunctional mediatorsExtracellular matrixDermal adipocytesMatrix homeostasisGenetic modelsNew targetsWntKey targetMechanisms of fibrosisFibrotic diseasesTherapeutic avenuesDermal remodelingExtracellular matrix expansionExcessive accumulationRemodelingFibrosis severitySkin fibrosisFibrotic remodelingDPP4 inhibitorsFibroblasts: Origins, definitions, and functions in health and disease
Plikus MV, Wang X, Sinha S, Forte E, Thompson SM, Herzog EL, Driskell RR, Rosenthal N, Biernaskie J, Horsley V. Fibroblasts: Origins, definitions, and functions in health and disease. Cell 2021, 184: 3852-3872. PMID: 34297930, PMCID: PMC8566693, DOI: 10.1016/j.cell.2021.06.024.Peer-Reviewed Original ResearchConceptsDiverse mesenchymal cellsComplex extracellular matrixCell fateCellular progenyTissue homeostasisCell cycleBiochemical cuesReversible plasticityExtracellular matrixPositional informationMesenchymal cellsSkeletal muscleTissue repairFibrotic disordersFibroblastsLineagesNicheProgenyHomeostasisPhenotypeOrgansFatePlasticityCellsFunctionThe LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation
Carley E, Stewart R, Zieman AG, Jalilian I, King DE, Zubek AE, Lin S, Horsley V, King MC. The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation. ELife 2021, 10: e58541. PMID: 33779546, PMCID: PMC8051949, DOI: 10.7554/elife.58541.Peer-Reviewed Original ResearchConceptsCell fateEpidermal cell fateLinker of nucleoskeletonCell fate decisionsEpidermal differentiation genesEpidermal differentiationDirect force transmissionEpidermal stem cellsCytoskeleton (LINC) complexLINC complexFate decisionsNuclear laminaType laminsDifferentiation genesIntegrin engagementForce transductionDifferentiation concomitantChemical signalsMechanotransduction pathwaysKeratinocyte progenitorsMolecular biosensorsStem cellsKeratinocyte differentiationDifferentiationMechanical input
2020
Dermal Adipocyte Lipolysis and Myofibroblast Conversion Are Required for Efficient Skin Repair
Shook BA, Wasko RR, Mano O, Rutenberg-Schoenberg M, Rudolph MC, Zirak B, Rivera-Gonzalez GC, López-Giráldez F, Zarini S, Rezza A, Clark DA, Rendl M, Rosenblum MD, Gerstein MB, Horsley V. Dermal Adipocyte Lipolysis and Myofibroblast Conversion Are Required for Efficient Skin Repair. Cell Stem Cell 2020, 26: 880-895.e6. PMID: 32302523, PMCID: PMC7853423, DOI: 10.1016/j.stem.2020.03.013.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingDermal adipocytesGenetic lineage tracingMammary gland biologyMature adipocytesGenetic mouse studiesAdipocyte-derived lipidsGenetic experimentsTissue homeostasisRNA sequencingLineage tracingECM-producing myofibroblastsDefective wound healingAdipocyte lipolysisMyofibroblast conversionAdipocyte functionEssential roleLipid releaseAdipocytesFatty acidsMacrophage inflammationInflammatory diseasesMultiple aspectsSkin repairMouse studiesSkin in the Game: Stem Cells in Repair, Cancer, and Homeostasis
Horsley V. Skin in the Game: Stem Cells in Repair, Cancer, and Homeostasis. Cell 2020, 181: 492-494. PMID: 32234524, DOI: 10.1016/j.cell.2020.03.019.Peer-Reviewed Original ResearchRegulated in Development and DNA Damage Responses 1 Prevents Dermal Adipocyte Differentiation and Is Required for Hair Cycle–Dependent Dermal Adipose Expansion
Rivera-Gonzalez GC, Klopot A, Sabin K, Baida G, Horsley V, Budunova I. Regulated in Development and DNA Damage Responses 1 Prevents Dermal Adipocyte Differentiation and Is Required for Hair Cycle–Dependent Dermal Adipose Expansion. Journal Of Investigative Dermatology 2020, 140: 1698-1705.e1. PMID: 32032578, PMCID: PMC7398827, DOI: 10.1016/j.jid.2019.12.033.Peer-Reviewed Original ResearchConceptsWhite adipose tissueAdipocyte precursor cellsAdipose tissueProtein kinase B signalingDNA damage response 1Loss of REDD1Precursor cellsProtein kinase BAdipogenic marker expressionKinase B signalingHigher lipid accumulationInguinal subcutaneous white adipose tissueGonadal white adipose tissueInterscapular brown adipose tissueSubcutaneous white adipose tissueWhite adipose tissue expansionNegative regulatorPostnatal day 18Wild-type miceAdipose tissue expansionKinase BRegulated developmentBrown adipose tissueHair growth cycleResponse 1
2019
Thin Skinned: Aged Adipocyte Atrophy Impacts Innate Immunity
Wasko RR, Horsley V. Thin Skinned: Aged Adipocyte Atrophy Impacts Innate Immunity. Trends In Immunology 2019, 40: 175-177. PMID: 30713009, DOI: 10.1016/j.it.2019.01.009.Peer-Reviewed Original Research
2018
Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair
Shook BA, Wasko RR, Rivera-Gonzalez GC, Salazar-Gatzimas E, López-Giráldez F, Dash BC, Muñoz-Rojas AR, Aultman KD, Zwick RK, Lei V, Arbiser JL, Miller-Jensen K, Clark DA, Hsia HC, Horsley V. Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair. Science 2018, 362 PMID: 30467144, PMCID: PMC6684198, DOI: 10.1126/science.aar2971.Peer-Reviewed Original ResearchConceptsDifferential gene expressionAdipocyte precursorsExtracellular matrix moleculesGene expressionTransplantation assaysMatrix moleculesFactor C.Factor 1Insulin-like growth factor-1Cell populationsTissue resilienceDistinct subpopulationsGrowth factor-1Profibrotic cellsTissue repairMultiple mouse modelsECM depositionSkin repairTissue dysfunctionProliferationMouse modelMyofibroblastsWoundingMacrophagesRepairAdipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation
Zwick RK, Rudolph MC, Shook BA, Holtrup B, Roth E, Lei V, Van Keymeulen A, Seewaldt V, Kwei S, Wysolmerski J, Rodeheffer MS, Horsley V. Adipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation. Nature Communications 2018, 9: 3592. PMID: 30181538, PMCID: PMC6123393, DOI: 10.1038/s41467-018-05911-0.Peer-Reviewed Original ResearchConceptsMouse mammary glandMilk-producing epithelial cellsTissue-specific rolesMammary glandAdipose growthLipid dynamicsGenetic tracingPhysiological examplesFunctional implicationsCellular mechanismsAdipocyte hypertrophyMature adipocytesEssential roleVivo analysisTissue functionMammary epitheliumAdipocytesEpithelial cellsAdipocyte precursorsSubsequent involutionMilk lipidsPrimary mechanismMechanismLipidomicsMilk fat productionAnatomical, Physiological, and Functional Diversity of Adipose Tissue
Zwick RK, Guerrero-Juarez CF, Horsley V, Plikus MV. Anatomical, Physiological, and Functional Diversity of Adipose Tissue. Cell Metabolism 2018, 27: 68-83. PMID: 29320711, PMCID: PMC6050204, DOI: 10.1016/j.cmet.2017.12.002.Peer-Reviewed Original ResearchConceptsStem cell quiescenceInnate immune barrierNon-traditional functionsFunctional diversityEpithelial stem cell quiescenceMammary glandCell quiescenceOrgan regenerationAdipocyte progenitorsHair folliclesNeighboring cellsMetabolic functionsRange of cancersNovel therapeutic approachesAdipose tissue depotsBacterial invasionAdipocytesProgenitorsAutoimmune disordersImmune barrierTherapeutic approachesClose associationAdipose tissueBone marrowTissue depots
2017
E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning
Rübsam M, Mertz AF, Kubo A, Marg S, Jüngst C, Goranci-Buzhala G, Schauss AC, Horsley V, Dufresne ER, Moser M, Ziegler W, Amagai M, Wickström SA, Niessen CM. E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning. Nature Communications 2017, 8: 1250. PMID: 29093447, PMCID: PMC5665913, DOI: 10.1038/s41467-017-01170-7.Peer-Reviewed Original ResearchPrdm1 Regulates Thymic Epithelial Function To Prevent Autoimmunity
Roberts NA, Adams BD, McCarthy NI, Tooze RM, Parnell SM, Anderson G, Kaech SM, Horsley V. Prdm1 Regulates Thymic Epithelial Function To Prevent Autoimmunity. The Journal Of Immunology 2017, 199: 1250-1260. PMID: 28701508, PMCID: PMC5544928, DOI: 10.4049/jimmunol.1600941.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, AntinuclearAutoantibodiesAutoimmunityEpithelial CellsForkhead Transcription FactorsGene Expression RegulationKeratin-14Lymphocyte ActivationMiceMice, Inbred C57BLMice, NudePositive Regulatory Domain I-Binding Factor 1Thymus GlandT-LymphocytesT-Lymphocytes, RegulatoryTranscription FactorsConceptsThymic epithelial cellsThymic epithelial functionT cellsSelf-reactive T cellsEpithelial functionRegulatory T cell developmentDevelopment of Foxp3Tissue-specific AgsMouse thymic epithelial cellsRegulatory T cellsMedullary thymic epithelial cellsAnti-nuclear AbsCell type-specific deletionT cell developmentDendritic cellsAutoantibody productionAutoimmune diseasesAutoimmune pathologyNude miceAutoimmunityTEC functionConditional deletionCrucial transcription factorMiceEpithelial cells
2016
Skin Adipocyte Stem Cell Self-Renewal Is Regulated by a PDGFA/AKT-Signaling Axis
Rivera-Gonzalez GC, Shook BA, Andrae J, Holtrup B, Bollag K, Betsholtz C, Rodeheffer MS, Horsley V. Skin Adipocyte Stem Cell Self-Renewal Is Regulated by a PDGFA/AKT-Signaling Axis. Cell Stem Cell 2016, 19: 738-751. PMID: 27746098, PMCID: PMC5135565, DOI: 10.1016/j.stem.2016.09.002.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipogenesisAnimalsCD24 AntigenCell ProliferationCell Self RenewalDermisGene Expression ProfilingHyperplasiaMice, Inbred C57BLModels, BiologicalPhosphatidylinositol 3-KinasesPlatelet-Derived Growth FactorProto-Oncogene Proteins c-aktReceptor, Platelet-Derived Growth Factor alphaSignal TransductionSkinStem CellsConceptsAdipocyte stem cellsAdipogenic programLipid-filled mature adipocytesStem Cell Self-RenewalCell Self-RenewalDistinct regulatory mechanismsASC proliferationPI3K/Akt2Stem cell populationWhite adipose tissueUnrecognized regulatorSelf-RenewalRegulatory mechanismsGenetic studiesMature adipocytesPDGFA expressionStem cellsCell populationsTissue growthProliferationActive mechanismDifferent WAT depotsHair growthMaintenanceAkt2CD301b+ Macrophages Are Essential for Effective Skin Wound Healing
Shook B, Xiao E, Kumamoto Y, Iwasaki A, Horsley V. CD301b+ Macrophages Are Essential for Effective Skin Wound Healing. Journal Of Investigative Dermatology 2016, 136: 1885-1891. PMID: 27287183, PMCID: PMC5727894, DOI: 10.1016/j.jid.2016.05.107.Peer-Reviewed Original ResearchConceptsSkin wound healingBarrier functionEssential inflammatory cellsAnti-inflammatory macrophagesWound healingSkin barrier functionSubpopulation of macrophagesEarly regenerative stageMultiple myeloid lineagesInflammatory cellsSyngeneic miceWound healing defectsMyeloid cellsCutaneous repairReparative processesSelective depletionPhenotype switchMacrophagesMyeloid lineageMiceMultiple cell typesHealingCD301bHealing defectsSkin repair