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 repair
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 inhibitorsThe 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 studiesRegulated 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 modelMyofibroblastsWoundingMacrophagesRepair
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
CD301b+ 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 repairPigment epithelium‐derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockade
Belinsky GS, Sreekumar B, Andrejecsk JW, Saltzman WM, Gong J, Herzog RI, Lin S, Horsley V, Carpenter TO, Chung C. Pigment epithelium‐derived factor restoration increases bone mass and improves bone plasticity in a model of osteogenesis imperfecta type VI via Wnt3a blockade. The FASEB Journal 2016, 30: 2837-2848. PMID: 27127101, PMCID: PMC4970601, DOI: 10.1096/fj.201500027r.Peer-Reviewed Original ResearchConceptsPigment epithelium-derived factorOsteogenesis imperfecta type VIWnt/β-catenin signalingBone massOI type VIΒ-catenin signalingAbility of PEDFTrabecular bone volume/total volumeType VIBone volume/total volumeWild-type miceEpithelium-derived factorBone plasticityPEDF-knockout miceMesenchymal stem cell commitmentBone volume fractionKO micePEDF peptidesStem cell commitmentFluorescent protein reporterCombination of Wnt3aMouse modelWnt modulatorsBone mineralizationMice
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 deletionNuclear–cytoskeletal linkages facilitate cross talk between the nucleus and intercellular adhesions
Stewart RM, Zubek AE, Rosowski KA, Schreiner SM, Horsley V, King MC. Nuclear–cytoskeletal linkages facilitate cross talk between the nucleus and intercellular adhesions. Journal Of Cell Biology 2015, 209: 403-418. PMID: 25963820, PMCID: PMC4427780, DOI: 10.1083/jcb.201502024.Peer-Reviewed Original ResearchConceptsIntercellular adhesionNuclear positionEpidermal tissue integrityLinker of nucleoskeletonCross talkPrimary mouse keratinocytesCytoskeleton (LINC) complexCytoplasmic cytoskeletonAdhesion functionMicrotubule networkDefective adhesionCytoskeletonSUN2Mouse keratinocytesTissue integrityFollicle structureEpidermal keratinocytesAdhesionNucleoskeletonCellsKeratinocytesAdhesion formationNucleusIntegrityComplexesTranscriptional Profiling of Ectoderm Specification to Keratinocyte Fate in Human Embryonic Stem Cells
Tadeu AM, Lin S, Hou L, Chung L, Zhong M, Zhao H, Horsley V. Transcriptional Profiling of Ectoderm Specification to Keratinocyte Fate in Human Embryonic Stem Cells. PLOS ONE 2015, 10: e0122493. PMID: 25849374, PMCID: PMC4388500, DOI: 10.1371/journal.pone.0122493.Peer-Reviewed Original ResearchConceptsHuman embryonic stem cellsEmbryonic stem cellsEctoderm specificationStem cellsHuman embryonic stem cell differentiationEmbryonic stem cell differentiationStem cell differentiationKeratinocyte fateEctoderm lineageEpidermal specificationTranscriptional regulationCandidate regulatorsTranscriptional profilingEpidermal developmentGrowth factor activityProtein aP2Keratinocyte developmentCell differentiationΓ-secretase inhibitor DAPTGenesFactor activityHomeostatic conditionsEpithelial tissuesInhibitor DAPTCell signature
2014
Defining dermal adipose tissue
Driskell RR, Jahoda CA, Chuong C, Watt FM, Horsley V. Defining dermal adipose tissue. Experimental Dermatology 2014, 23: 629-631. PMID: 24841073, PMCID: PMC4282701, DOI: 10.1111/exd.12450.Peer-Reviewed Original ResearchConceptsDevelopment of adipocytesSubcutaneous adipose tissue developmentHair follicle regenerationAdipose tissue developmentDermal adipose tissueTissue developmentEpidermal homeostasisLipid-filled cellsFollicle regenerationCommon precursorRole of adipocytesAdipocytesAdipose tissueDermal fibroblastsDermal white adipose tissueWhite adipose tissueHair folliclesSubcutaneous adiposeInvertebratesCellsTissueRecent dataSpeciesHomeostasisHypodermisPygo2 regulates β-catenin–induced activation of hair follicle stem/progenitor cells and skin hyperplasia
Sun P, Watanabe K, Fallahi M, Lee B, Afetian ME, Rheaume C, Wu D, Horsley V, Dai X. Pygo2 regulates β-catenin–induced activation of hair follicle stem/progenitor cells and skin hyperplasia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 10215-10220. PMID: 24982158, PMCID: PMC4104891, DOI: 10.1073/pnas.1311395111.Peer-Reviewed Original ResearchConceptsStem cell activationStem/progenitor cellsEarly progenitor cellsProgenitor cellsWnt/β-catenin targetsΒ-catenin functionStem cellsTumor suppressor protein p53Β-catenin targetsWnt/β-catenin functionsCell cycle entryAdult stem cellsHair follicle stem cellsSuppressor protein p53Chromatin factorsFollicle stem cellsProgenitor cell compartmentHomeobox proteinEpigenetic mechanismsCell activationCycle entryDownstream eventsPathway functionOrgan regenerationImportant regulatorCalcineurin/Nfatc1 signaling links skin stem cell quiescence to hormonal signaling during pregnancy and lactation
Goldstein J, Fletcher S, Roth E, Wu C, Chun A, Horsley V. Calcineurin/Nfatc1 signaling links skin stem cell quiescence to hormonal signaling during pregnancy and lactation. Genes & Development 2014, 28: 983-994. PMID: 24732379, PMCID: PMC4018496, DOI: 10.1101/gad.236554.113.Peer-Reviewed Original ResearchConceptsStem cell quiescenceStem cell nicheHair follicle (HF) SCsTranscription factor nuclear factorJAK/STAT5Hormonal signalingMolecular circuitryActivated T cells c1Phosphatase calcineurinCell nicheSC quiescenceCell quiescenceT cells c1Calcineurin/NFATc1Function experimentsGenetic changesCanonical activationPharmacological lossPRL injectionsSC activationProlactin receptorMost tissuesTissue environmentHF SCsNuclear factor
2013
Notch signaling represses p63 expression in the developing surface ectoderm
Tadeu AM, Horsley V. Notch signaling represses p63 expression in the developing surface ectoderm. Development 2013, 140: 3777-3786. PMID: 23924630, PMCID: PMC3754476, DOI: 10.1242/dev.093948.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBody PatterningCell DifferentiationEctodermEmbryonic Stem CellsEpidermal CellsEpidermisGene Expression Regulation, DevelopmentalHumansKeratin-14KeratinocytesMiceModels, BiologicalPhosphoproteinsReceptors, NotchRepressor ProteinsSignal TransductionStem CellsTrans-ActivatorsTranscription FactorsTumor Suppressor ProteinsConceptsHuman embryonic stem cellsProgenitor cellsMouse embryosKeratinocyte lineageProgenitor cell specificationEmbryonic stem cellsNegative regulatory roleKeratinocyte fateCell specificationEctodermal specificationInhibition of NotchTranscriptional changesMolecular controlNotch signalingRegulatory roleSurface ectodermP63 expressionStem cellsCoordinated sequenceLineagesMature epidermisEmbryosKeratin 14ExpressionCells