2023
IL-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 repairSingle cell transcriptomic landscape of diabetic foot ulcers
Theocharidis G, Thomas BE, Sarkar D, Mumme HL, Pilcher WJR, Dwivedi B, Sandoval-Schaefer T, Sîrbulescu RF, Kafanas A, Mezghani I, Wang P, Lobao A, Vlachos IS, Dash B, Hsia HC, Horsley V, Bhasin SS, Veves A, Bhasin M. Single cell transcriptomic landscape of diabetic foot ulcers. Nature Communications 2022, 13: 181. PMID: 35013299, PMCID: PMC8748704, DOI: 10.1038/s41467-021-27801-8.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersCell Adhesion MoleculesChitinase-3-Like Protein 1Diabetes MellitusDiabetic FootEndothelial CellsExome SequencingFibroblastsGene Expression RegulationHigh-Throughput Nucleotide SequencingHumansHypoxia-Inducible Factor 1, alpha SubunitKeratinocytesLeukocytesMacrophagesMatrix Metalloproteinase 1Matrix Metalloproteinase 11Matrix Metalloproteinase 3Single-Cell AnalysisSkinTranscriptomeWound HealingConceptsDiabetic foot ulcerationSpatial transcriptomicsSingle-cell transcriptomic landscapeSingle-cell RNA sequencingPeripheral blood mononuclear cellsBlood mononuclear cellsDiabetic foot ulcersM1 macrophage polarizationNovel therapeutic approachesTranscriptomic landscapeWound healing microenvironmentRNA sequencingDFU patientsDevastating complicationFoot ulcerationDFU healingFoot ulcersDFU treatmentMononuclear cellsM1 macrophagesM2 macrophagesMacrophage polarizationTherapeutic approachesSame patientHigh abundance
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 inhibitors
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 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 modelMyofibroblastsWoundingMacrophagesRepair
2017
Tregs Expand the Skin Stem Cell Niche
Horsley V, Naik S. Tregs Expand the Skin Stem Cell Niche. Developmental Cell 2017, 41: 455-456. PMID: 28586641, DOI: 10.1016/j.devcel.2017.05.020.Peer-Reviewed Original Research
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
2015
Loss of endogenous Nfatc1 reduces the rate of DMBA/TPA-induced skin tumorigenesis
Goldstein J, Roth E, Roberts N, Zwick R, Lin S, Fletcher S, Tadeu A, Wu C, Beck A, Zeiss C, Suárez-Fariñas M, Horsley V. Loss of endogenous Nfatc1 reduces the rate of DMBA/TPA-induced skin tumorigenesis. Molecular Biology Of The Cell 2015, 26: 3606-3614. PMID: 26310443, PMCID: PMC4603931, DOI: 10.1091/mbc.e15-05-0282.Peer-Reviewed Original ResearchConceptsDMBA/TPA-induced skin tumorigenesisFollicular stem cellsSkin tumorigenesisDMBA metabolismDMBA-induced DNA damageSquamous cell carcinoma formationSkin squamous cell carcinomaStem cellsSquamous cell carcinomaEndogenous expressionRate of tumorigenesisImmunosuppressive therapyCalcineurin inhibitorsCell carcinomaSkin tumorsHigh incidenceCarcinoma formationHair follicle bulge stem cellsMiceNFATc1Tumor initiationActive NFATc1Suppress tumorigenesisBulge stem cellsInducible deletion
2014
Adipocytes in Skin Health and Disease
Rivera-Gonzalez G, Shook B, Horsley V. Adipocytes in Skin Health and Disease. Cold Spring Harbor Perspectives In Medicine 2014, 4: a015271. PMID: 24591537, PMCID: PMC3935392, DOI: 10.1101/cshperspect.a015271.Peer-Reviewed Original ResearchConceptsCutaneous biologyDermal adipocytesHair follicle growthTissue homeostasisDermal adipose tissueCellular basisRole of adipocytesAdipocytesHair cycleRegenerative capacityBiologyClinical manifestationsCutaneous diseaseReservoir of energyDermal compartmentAdipose tissueFollicle growthPotential roleSkin healthRecent studiesStructural supportWound healingDiseaseDynamic changesHomeostasisChapter Four Epithelial Stem Cells in Adult Skin
Tadeu AM, Horsley V. Chapter Four Epithelial Stem Cells in Adult Skin. Current Topics In Developmental Biology 2014, 107: 109-131. PMID: 24439804, PMCID: PMC5595246, DOI: 10.1016/b978-0-12-416022-4.00004-4.Peer-Reviewed Original ResearchConceptsAdult skin epitheliumTissue-specific stem cellsDifferent stem cell populationsStem cellsStem cell nicheNormal skin homeostasisStem cell populationStem cell activityCell nicheEpithelial stem cellsSkin homeostasisAbnormal regulationCell populationsAdult skinSkin epitheliumExtrinsic componentsEnvironmental aggressionsCellsNicheAdult lifeHomeostasisFirst lineRegulationRecent effortsCell activity
2013
Intradermal adipocytes mediate fibroblast recruitment during skin wound healing
Schmidt BA, Horsley V. Intradermal adipocytes mediate fibroblast recruitment during skin wound healing. Development 2013, 140: 1517-1527. PMID: 23482487, PMCID: PMC3596993, DOI: 10.1242/dev.087593.Peer-Reviewed Original Research
2012
IL-22 Promotes Fibroblast-Mediated Wound Repair in the Skin
McGee HM, Schmidt BA, Booth CJ, Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA, Horsley V. IL-22 Promotes Fibroblast-Mediated Wound Repair in the Skin. Journal Of Investigative Dermatology 2012, 133: 1321-1329. PMID: 23223145, PMCID: PMC3610794, DOI: 10.1038/jid.2012.463.Peer-Reviewed Original ResearchConceptsIL-22Immune cellsCytokine IL-22Epithelial cellsWound repairIL-22 signalingDermal compartmentFull-thickness woundingAcute injuryPeripheral tissuesSkin wound repairEpithelial regenerationMyofibroblast differentiationSkin woundingEpidermal barrierExtracellular matrix gene expressionMatrix gene expressionInjuryVivo roleSkin repairMiceUnidentified roleFibroblastsRepairUnidirectional signalingHome sweet home: skin stem cell niches
Goldstein J, Horsley V. Home sweet home: skin stem cell niches. Cellular And Molecular Life Sciences 2012, 69: 2573-2582. PMID: 22410738, PMCID: PMC3449145, DOI: 10.1007/s00018-012-0943-3.Peer-Reviewed Original Research
2011
Adipocyte Lineage Cells Contribute to the Skin Stem Cell Niche to Drive Hair Cycling
Festa E, Fretz J, Berry R, Schmidt B, Rodeheffer M, Horowitz M, Horsley V. Adipocyte Lineage Cells Contribute to the Skin Stem Cell Niche to Drive Hair Cycling. Cell 2011, 146: 761-771. PMID: 21884937, PMCID: PMC3298746, DOI: 10.1016/j.cell.2011.07.019.Peer-Reviewed Original ResearchConceptsAdipocyte lineage cellsStem cell nicheStem cell activityLineage cellsCell nicheSkin stem cell nichesStem cell functionEpithelial stem cell nicheStem cell activationEpithelial stem cell functionSkin stem cellsTissue homeostasisNiche cellsFunctional analysisAdipogenic cellsSkin homeostasisMammalian skinTransplantation experimentsStem cellsPrecursor cellsHair cyclingCell functionAdipocyte cellsNicheFunctional tissue
2008
More than one way to skin . . .
Fuchs E, Horsley V. More than one way to skin . . . Genes & Development 2008, 22: 976-985. PMID: 18413712, PMCID: PMC2732395, DOI: 10.1101/gad.1645908.Peer-Reviewed Original ResearchConceptsStem cellsMultiple signaling networksNormal tissue homeostasisStem cell nicheStem cell populationResident stem cellsEpithelial-mesenchymal interactionsCell populationsCell fateSignaling networksSpecific lineagesTissue homeostasisCell nicheEpithelial stem cellsEpithelial lineageRecent cluesNormal homeostasisEpithelial tissuesLineagesWound repairHomeostasisCellsHair folliclesNicheFateNFATc1 Balances Quiescence and Proliferation of Skin Stem Cells
Horsley V, Aliprantis AO, Polak L, Glimcher LH, Fuchs E. NFATc1 Balances Quiescence and Proliferation of Skin Stem Cells. Cell 2008, 132: 299-310. PMID: 18243104, PMCID: PMC2546702, DOI: 10.1016/j.cell.2007.11.047.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD34BiomarkersCell NucleusCell ProliferationCells, CulturedCyclin-Dependent Kinase 4CyclosporineDown-RegulationEmbryo, MammalianGene DeletionGene ExpressionGene Expression Regulation, DevelopmentalGenes, ReporterHair FollicleImmunohistochemistryImmunosuppressive AgentsMiceMice, KnockoutMice, NudeMorphogenesisNFATC Transcription FactorsRetroviridaeRNA, MessengerSkinSkin TransplantationStem CellsTranscription FactorsTransgenesTransplantation, HomologousConceptsStem cellsHair growthCell quiescenceStem cell quiescenceExcessive hair growthFollicular growthNFATc1 signalingHair follicle stem cellsFollicle stem cellsGene ablationQuiescent adult stem cellsAdult stem cellsNFATc1Skin stem cellsFunctional roleCellsTissue homeostasisProliferationPatientsInjury