2023
Injury prevents Ras mutant cell expansion in mosaic skin
Gallini S, Annusver K, Rahman N, Gonzalez D, Yun S, Matte-Martone C, Xin T, Lathrop E, Suozzi K, Kasper M, Greco V. Injury prevents Ras mutant cell expansion in mosaic skin. Nature 2023, 619: 167-175. PMID: 37344586, PMCID: PMC10322723, DOI: 10.1038/s41586-023-06198-y.Peer-Reviewed Original ResearchConceptsWild-type cellsRas family proteinsCell cycle inhibitor p21Family proteinsOncogenic RasGenetic approachesMosaic tissuesInhibition of EGFRInhibitor p21EGFR ligandsEGFR pathwayCell expansionAberrant growthConstitutive lossDifferential activationParacrine secretionAbsence of injuryCellsCompetitive balanceInjury repairHealthy skinInjurySkinProteinPathwayMechanisms of skin vascular maturation and maintenance captured by longitudinal imaging of live mice
Kam C, Singh I, Gonzalez D, Matte-Martone C, Solá P, Solanas G, Bonjoch J, Marsh E, Hirschi K, Greco V. Mechanisms of skin vascular maturation and maintenance captured by longitudinal imaging of live mice. Cell 2023, 186: 2345-2360.e16. PMID: 37167971, PMCID: PMC10225355, DOI: 10.1016/j.cell.2023.04.017.Peer-Reviewed Original ResearchConceptsAdult endothelial cellsNeonatal endothelial cellsEndothelial cellsVascular maturationAdult homeostasisOrgan growthAdult maintenanceHomeostasisLive miceVessel regressionFundamental mechanismsGlobal ablationLocal ablationMaturationNetwork perfusionVascular plexusBlood vesselsLongitudinal imagingVessel repairMaintenanceVascular architecturePlexusFunctional networksMiceMechanismLive imaging reveals chromatin compaction transitions and dynamic transcriptional bursting during stem cell differentiation in vivo
May D, Yun S, Gonzalez D, Park S, Chen Y, Lathrop E, Cai B, Xin T, Zhao H, Wang S, Gonzalez L, Cockburn K, Greco V. Live imaging reveals chromatin compaction transitions and dynamic transcriptional bursting during stem cell differentiation in vivo. ELife 2023, 12: e83444. PMID: 36880644, PMCID: PMC10027315, DOI: 10.7554/elife.83444.Peer-Reviewed Original ResearchConceptsStem cell differentiationCell differentiationStem cell compartmentCompaction changesChromatin compaction statesDynamic transcriptional statesCell compartmentChromatin architectureCell cycle statusChromatin rearrangementNascent RNATranscriptional burstingTranscriptional statesLive imagingTissue contextGene expressionDifferentiating cellsGlobal remodelingIndividual cellsCycle statusStem cellsDifferentiation statusDifferentiationCellsMorphological changes
2022
Gradual differentiation uncoupled from cell cycle exit generates heterogeneity in the epidermal stem cell layer
Cockburn K, Annusver K, Gonzalez D, Ganesan S, May D, Mesa K, Kawaguchi K, Kasper M, Greco V. Gradual differentiation uncoupled from cell cycle exit generates heterogeneity in the epidermal stem cell layer. Nature Cell Biology 2022, 24: 1692-1700. PMID: 36357619, PMCID: PMC9729105, DOI: 10.1038/s41556-022-01021-8.Peer-Reviewed Original ResearchConceptsCell cycle exitCycle exitStem cell layerUndifferentiated stem cellsStem cell compartmentDaughter cellsDifferentiated populationsDifferentiation genesTranscriptional changesCell divisionMultiple progenitorsStemness genesCells transitStem cellsCell compartmentCell layerCell poolDifferentiationRegenerative tissueGenesSkin epidermisGradual differentiationMulti-day processesCells
2021
Skin-resident immune cells actively coordinate their distribution with epidermal cells during homeostasis
Park S, Matte-Martone C, Gonzalez DG, Lathrop EA, May DP, Pineda CM, Moore JL, Boucher JD, Marsh E, Schmitter-Sánchez A, Cockburn K, Markova O, Bellaïche Y, Greco V. Skin-resident immune cells actively coordinate their distribution with epidermal cells during homeostasis. Nature Cell Biology 2021, 23: 476-484. PMID: 33958758, PMCID: PMC8603572, DOI: 10.1038/s41556-021-00670-5.Peer-Reviewed Original ResearchConceptsDendritic epidermal T cellsLangerhans cellsCell typesEpithelial cellsDifferent cell typesMultiple cell typesLive adult miceGTPase Rac1Skin-resident immune cellsNon-random spatial distributionDistribution of LCContinuous turnoverEpidermal cellsEpidermal T cellsIndividual cellsCellular mechanismsEnvironmental insultsHomeostasisBasal epithelial cellsImmune cellsT cellsAdult miceCellsProper architectureEpidermisCombined liver–cytokine humanization comes to the rescue of circulating human red blood cells
Song Y, Shan L, Gbyli R, Liu W, Strowig T, Patel A, Fu X, Wang X, Xu ML, Gao Y, Qin A, Bruscia EM, Tebaldi T, Biancon G, Mamillapalli P, Urbonas D, Eynon E, Gonzalez DG, Chen J, Krause DS, Alderman J, Halene S, Flavell RA. Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells. Science 2021, 371: 1019-1025. PMID: 33674488, PMCID: PMC8292008, DOI: 10.1126/science.abe2485.Peer-Reviewed Original ResearchConceptsRed blood cellsBlood cellsHuman sickle cell diseaseSickle cell diseaseImmunodeficient murine modelKupffer cell densityBone marrow failureMISTRG miceIntrasplenic injectionSCD pathologyCell diseaseMurine modelComplement C3RBC survivalVivo modelHuman cytokinesPreclinical testingHematopoietic stem cellsHuman red blood cellsMarrow failureFumarylacetoacetate hydrolase geneHuman erythropoiesisHuman liverHuman hepatocytesMice
2019
Hair follicle regeneration suppresses Ras-driven oncogenic growth
Pineda CM, Gonzalez DG, Matte-Martone C, Boucher J, Lathrop E, Gallini S, Fons NR, Xin T, Tai K, Marsh E, Nguyen DX, Suozzi KC, Beronja S, Greco V. Hair follicle regeneration suppresses Ras-driven oncogenic growth. Journal Of Cell Biology 2019, 218: 3212-3222. PMID: 31488583, PMCID: PMC6781447, DOI: 10.1083/jcb.201907178.Peer-Reviewed Original ResearchConceptsHair folliclesHras mutationsOncogenic growthHair follicle stem cellsSkin hair folliclesTumor developmentFollicle stem cellsHair follicle regenerationSkin epitheliumSecondary mutationsBenign outgrowthFolliclesStem cellsTissueCertain tissuesFollicle regenerationCellsContinuous tissueWild-type neighborsDistinct mechanismsDifferent outcomesMutationsEnhanced capacityInjuryIn vivo dynamics of T cells and their interactions with dendritic cells in mouse cutaneous graft-versus-host disease
Morin-Zorman S, Wysocki C, Zhu J, Li H, Zorman S, Matte-Martone C, Kisanga E, McNiff J, Jain D, Gonzalez D, Rothstein DM, Lakkis FG, Haberman A, Shlomchik WD. In vivo dynamics of T cells and their interactions with dendritic cells in mouse cutaneous graft-versus-host disease. Blood Advances 2019, 3: 2082-2092. PMID: 31296496, PMCID: PMC6650737, DOI: 10.1182/bloodadvances.2019000227.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCD11c AntigenCell CommunicationDendritic CellsDisease Models, AnimalFluorescent Antibody TechniqueGene ExpressionGenes, ReporterGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHistocompatibility Antigens Class IImmunophenotypingLymphocyte DepletionMiceMice, TransgenicProtein BindingReceptors, Antigen, T-CellSkin DiseasesT-Lymphocyte SubsetsT-LymphocytesTransplantation, HomologousConceptsDonor dendritic cellsCD8 cellsT cellsGVHD lesionsHost diseaseCD4 cellsDendritic cellsAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationMajority of CD4Dynamics of CD4Stem cell transplantationCutaneous graftAntibody infusionCell transplantationMyeloid cellsIntravital microscopyAcute deletionMajor causeLesionsTarget tissuesCD103CD4InfusionMHCII
2018
Nonredundant Roles of IL-21 and IL-4 in the Phased Initiation of Germinal Center B Cells and Subsequent Self-Renewal Transitions.
Gonzalez DG, Cote CM, Patel JR, Smith CB, Zhang Y, Nickerson KM, Zhang T, Kerfoot SM, Haberman AM. Nonredundant Roles of IL-21 and IL-4 in the Phased Initiation of Germinal Center B Cells and Subsequent Self-Renewal Transitions. The Journal Of Immunology 2018, 201: 3569-3579. PMID: 30446568, PMCID: PMC6289626, DOI: 10.4049/jimmunol.1500497.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisB-LymphocytesCell DifferentiationCell Self RenewalCells, CulturedGerminal CenterInterleukin-4InterleukinsLymphocyte ActivationMiceMice, KnockoutParacrine CommunicationProto-Oncogene Proteins c-bcl-6Receptors, Interleukin-21Signal TransductionSTAT6 Transcription FactorT-Lymphocytes, Helper-InducerConceptsIL-21IL-4B cellsIL-21RCytokine IL-21Costimulatory molecule expressionB cell folliclesIL-21 signalingGC B cell developmentNonredundant roleGerminal center B cellsMurine model systemGC B cellsMolecule expressionPhenotypic maturationB cell developmentCell expressionCytokine signalsB cell transitionCombined absenceSubsequent maturationCell migrationCell developmentFlexible fate determination ensures robust differentiation in the hair follicle
Xin T, Gonzalez D, Rompolas P, Greco V. Flexible fate determination ensures robust differentiation in the hair follicle. Nature Cell Biology 2018, 20: 1361-1369. PMID: 30420661, PMCID: PMC6314017, DOI: 10.1038/s41556-018-0232-y.Peer-Reviewed Original ResearchConceptsSingle-cell levelStem cellsStem cell differentiationGerm stem cellsTissue architectureMultiple cell typesFate determinationDetermination mechanismTissue homeostasisSame stem cellsCommon progenitorDifferentiation outcomesDifferentiation stimuliDifferentiation lineageCell differentiationCell typesNormal differentiationWnt activationHair folliclesUnanticipated flexibilityDifferentiationRobust differentiationProgenitorsCellsUninjured conditionPositional Stability and Membrane Occupancy Define Skin Fibroblast Homeostasis In Vivo
Marsh E, Gonzalez DG, Lathrop EA, Boucher J, Greco V. Positional Stability and Membrane Occupancy Define Skin Fibroblast Homeostasis In Vivo. Cell 2018, 175: 1620-1633.e13. PMID: 30415836, PMCID: PMC7605015, DOI: 10.1016/j.cell.2018.10.013.Peer-Reviewed Original ResearchConceptsCore cellular mechanismsFibroblast homeostasisRac1-dependent mannerNeighboring fibroblastsMembrane occupancyMembrane extensionsNucleus organizationCellular mechanismsHomeostasisFibroblast membranesAbsence of migrationFibroblastsCell occupancySkin fibroblastsProgressive accumulationVivoStructural componentsLifespan of miceLive miceOccupancyMicePositional stabilityMembraneLifespanAccumulationHomeostatic Epidermal Stem Cell Self-Renewal Is Driven by Local Differentiation
Mesa KR, Kawaguchi K, Cockburn K, Gonzalez D, Boucher J, Xin T, Klein AM, Greco V. Homeostatic Epidermal Stem Cell Self-Renewal Is Driven by Local Differentiation. Cell Stem Cell 2018, 23: 677-686.e4. PMID: 30269903, PMCID: PMC6214709, DOI: 10.1016/j.stem.2018.09.005.Peer-Reviewed Original Research
2017
Correction of aberrant growth preserves tissue homeostasis
Brown S, Pineda CM, Xin T, Boucher J, Suozzi KC, Park S, Matte-Martone C, Gonzalez DG, Rytlewski J, Beronja S, Greco V. Correction of aberrant growth preserves tissue homeostasis. Nature 2017, 548: 334-337. PMID: 28783732, PMCID: PMC5675114, DOI: 10.1038/nature23304.Peer-Reviewed Original ResearchTissue-scale coordination of cellular behaviour promotes epidermal wound repair in live mice
Park S, Gonzalez DG, Guirao B, Boucher JD, Cockburn K, Marsh ED, Mesa KR, Brown S, Rompolas P, Haberman AM, Bellaïche Y, Greco V. Tissue-scale coordination of cellular behaviour promotes epidermal wound repair in live mice. Nature Cell Biology 2017, 19: 155-163. PMID: 28248302, PMCID: PMC5581297, DOI: 10.1038/ncb3472.Peer-Reviewed Original ResearchTissue-scale organizationEpidermal wound repairRegional coexistenceCellular behaviorDifferentiated cellsEpithelial behaviorUndamaged cellsProliferation functionTissue architectureHomeostatic functionsDifferentiation changesLive mammalsLive miceWound repairTissue repairProliferative zoneHomeostatic behaviorCellsSkin repairSpatiotemporal dynamicsMammalsWoundsMiceRepairMigration