2025
Single cell RNA seq reveals the pro-regenerative phenotype of thrombospondin-2 deficient dermal fibroblasts
Huang Y, Wang N, Xing H, Gao D, Hsia H, Raredon M, Kyriakides T. Single cell RNA seq reveals the pro-regenerative phenotype of thrombospondin-2 deficient dermal fibroblasts. Scientific Reports 2025, 15: 32304. PMID: 40897801, PMCID: PMC12405501, DOI: 10.1038/s41598-025-15839-3.Peer-Reviewed Original ResearchConceptsSingle cell RNA-seqSingle-cell RNA sequencingIn silico analysisThrombospondin-2Gene expression profilesDifferential signaling pathwaysDermal fibroblastsRNA-seqKO fibroblastsScRNA-seqSilico analysisRNA sequencingPro-survivalSignaling pathwayExpression profilesCell communicationTissue developmentCell heterogeneityPro-regenerative phenotypeSkin fibroblastsPro-regenerative featuresSOX10Schwann precursor cellsFibroblastsCellsIdentifying genes underlying parallel evolution of stromal resistance to placental and cancer invasion
Suhail Y, Du W, Afzal J, Wagner G, Kshitiz. Identifying genes underlying parallel evolution of stromal resistance to placental and cancer invasion. Npj Systems Biology And Applications 2025, 11: 95. PMID: 40847025, PMCID: PMC12373941, DOI: 10.1038/s41540-025-00577-z.Peer-Reviewed Original ResearchGene setsPlacental invasionHuman cancersResistance to invasionStromal genesStromal regulationCausal genesTranscriptional regulationHuman endometrial fibroblastsGenesStromal resistanceEpithelial invasionCancer malignancyEndometrial fibroblastsHuman fibroblastsCancer disseminationCancer invasionInvasionCancerFibroblastsJDP2EutheriansStage transitionsHypoxia-induced Wnt5a-secreting fibroblasts promote colon cancer progression
Harada A, Yasumizu Y, Harada T, Fumoto K, Sato A, Maehara N, Sada R, Matsumoto S, Nishina T, Takeda K, Morii E, Kayama H, Kikuchi A. Hypoxia-induced Wnt5a-secreting fibroblasts promote colon cancer progression. Nature Communications 2025, 16: 3653. PMID: 40246836, PMCID: PMC12006413, DOI: 10.1038/s41467-025-58748-9.Peer-Reviewed Original ResearchConceptsColon cancer progressionSingle-cell RNA-seq dataCancer progressionEndothelial cellsRNA-seq dataColon cancer aggressivenessSuppression of angiogenesisColon cancer growthColon cancer formationCancer aggressivenessInflammatory fibroblastsVEGF receptor1Cancer growthPromote tumorigenesisCancer formationWnt5aMeta-analysisWnt ligandsLuminal sideFibroblast subtypesColonHypoxic environmentFibroblastsCells
2024
Direct cardiac reprogramming via combined CRISPRa-mediated endogenous Gata4 activation and exogenous Mef2c and Tbx5 expression
Huang P, Xu J, Keepers B, Xie Y, Near D, Xu Y, Hua J, Spurlock B, Ricketts S, Liu J, Wang L, Qian L. Direct cardiac reprogramming via combined CRISPRa-mediated endogenous Gata4 activation and exogenous Mef2c and Tbx5 expression. Molecular Therapy - Nucleic Acids 2024, 35: 102390. PMID: 39720701, PMCID: PMC11666955, DOI: 10.1016/j.omtn.2024.102390.Peer-Reviewed Original ResearchActivity of endogenous factorsDirect cardiac reprogrammingInduced cardiomyocytesCardiac reprogrammingExpression of cardiac transcription factorsCardiac transcription factorsTranscription factorsReprogramming of fibroblastsSingle-guide RNAViral toxicityViral vectorsExogenous transcription factorsImmune responseEpigenetic barriersGATA4 activityRegenerative purposesClinical applicationEndogenous factorsEndogenous transcription factorsGenomic mutationsExogenous expressionReprogrammingFibroblastsEndogenous gene expressionHuman fibroblastsAbsence of ATG9A and synaptophysin demixing on Rab5 mutation-induced giant endosomes
Choi J, Wu Y, Park D. Absence of ATG9A and synaptophysin demixing on Rab5 mutation-induced giant endosomes. Molecular Brain 2024, 17: 63. PMID: 39223639, PMCID: PMC11367939, DOI: 10.1186/s13041-024-01132-3.Peer-Reviewed Original ResearchConceptsGiant endosomesFormation of enlarged endosomesAutophagy-related (ATG) proteinsPool of vesiclesIntegral membrane proteinsRab5 mutantsEnlarged endosomesCore autophagy-related (ATG) proteinsEndosomal localizationIntracellular sortingMembrane proteinsEndocytic originEndosomesATG9ARab5ProteinVesiclesMutantsSegregation mechanismSynapsinCo-assemblyNerve terminalsSynaptophysinFibroblastsCellsCancer cell – Fibroblast crosstalk via HB-EGF, EGFR, and MAPK signaling promotes the expression of macrophage chemo-attractants in squamous cell carcinoma
Giangreco G, Rullan A, Naito Y, Biswas D, Liu Y, Hooper S, Nenclares P, Bhide S, Chon U Cheang M, Chakravarty P, Hirata E, Swanton C, Melcher A, Harrington K, Sahai E. Cancer cell – Fibroblast crosstalk via HB-EGF, EGFR, and MAPK signaling promotes the expression of macrophage chemo-attractants in squamous cell carcinoma. IScience 2024, 27: 110635. PMID: 39262776, PMCID: PMC11387794, DOI: 10.1016/j.isci.2024.110635.Peer-Reviewed Original ResearchTumor microenvironmentSquamous cell carcinoma cohortCancer cellsMacrophage chemo-attractantsSquamous cell carcinomaTumor-stroma crosstalkRecruitment of macrophagesExpression of CSF2Prognostic significanceCarcinoma cohortCell carcinomaPatient prognosisHB-EGFStromal fibroblastsCancer outcomesCancer progressionCancerMAPK signalingIndicator of signalingChemo-attractantsCellsFibroblastsCarcinomaExpressionEGFRDirect conversion of cardiac fibroblasts into endothelial-like cells using Sox17 and Erg
Farber G, Dong Y, Wang Q, Rathod M, Wang H, Dixit M, Keepers B, Xie Y, Butz K, Polacheck W, Liu J, Qian L. Direct conversion of cardiac fibroblasts into endothelial-like cells using Sox17 and Erg. Nature Communications 2024, 15: 4170. PMID: 38755186, PMCID: PMC11098819, DOI: 10.1038/s41467-024-48354-6.Peer-Reviewed Original ResearchConceptsCardiac fibroblastsEndothelial cellsEndothelial-like cellsIn vivoRepair injured tissuesFunction in vitroInduced endothelial cellsConversion of cardiac fibroblastsInfarct siteReprogramming strategiesMyocardial infarction siteReprogramming approachInjured tissueInjury resultsVascular perfusionEndothelial-likeScar regionPhysiological function in vitroIn vitroOrgan-specificFibroblastsHeterogeneous populationCellsReprogrammingFibroblast expression of transmembrane protein smoothened governs microenvironment characteristics after acute kidney injury
Gui Y, Fu H, Palanza Z, Tao J, Lin Y, Min W, Qiao Y, Bonin C, Hargis G, Wang Y, Yang P, Kreutzer D, Wang Y, Liu Y, Yu Y, Liu Y, Zhou D. Fibroblast expression of transmembrane protein smoothened governs microenvironment characteristics after acute kidney injury. Journal Of Clinical Investigation 2024, 134: e165836. PMID: 38713523, PMCID: PMC11213467, DOI: 10.1172/jci165836.Peer-Reviewed Original ResearchNidogen-1Expression of transmembrane proteinsCell-matrix interactionsAcute kidney injuryExtracellular matrix proteinsWnt Signaling PathwayGlobal proteomeHedgehog signalingTransmembrane proteinsTubular cell apoptosisSignaling pathwayCell apoptosisMatrix proteinsIntegrin B1Kidney fibroblastsMesenchymal cell activationKidney injuryHedgehogProteinMitigate acute kidney injurySMOPreserved kidney functionAcute kidney injury pathogenesisFibroblastsPhosphoproteomeCharting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling
Cadinu P, Sivanathan K, Misra A, Xu R, Mangani D, Yang E, Rone J, Tooley K, Kye Y, Bod L, Geistlinger L, Lee T, Mertens R, Ono N, Wang G, Sanmarco L, Quintana F, Anderson A, Kuchroo V, Moffitt J, Nowarski R. Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling. Cell 2024, 187: 2010-2028.e30. PMID: 38569542, PMCID: PMC11017707, DOI: 10.1016/j.cell.2024.03.013.Peer-Reviewed Original ResearchConceptsMultiplexed error-robust fluorescence in situ hybridizationFluorescence in situ hybridizationSpatial organizationCell-cell interactionsDiverse cell populationsHealthy gutMouse colitis modelExpression profilesBiogeographyGutNon-immune cellsGut inflammationSpatial remodelingInflammation-associated fibroblastsTissue neighborhoodsInflammation-induced remodelingCell populationsFibroblastsImmune cellsCellsColitis modelUlcerative colitisFibroblastic originStage progressionExpression
2023
Experimental and phylogenetic evidence for correlated gene expression evolution in endometrial and skin fibroblasts
Dighe A, Maziarz J, Ibrahim-Hashim A, Gatenby R, Kshitiz, Levchenko A, Wagner G. Experimental and phylogenetic evidence for correlated gene expression evolution in endometrial and skin fibroblasts. IScience 2023, 27: 108593. PMID: 38174318, PMCID: PMC10762354, DOI: 10.1016/j.isci.2023.108593.Peer-Reviewed Original ResearchGene expression changesGene expression evolutionEndometrial stromal fibroblastsExpression evolutionExpression changesCell typesGene expressionSimilar gene expression changesSubstantial gene expression changesGene expression profilesSkin fibroblastsMultiple cell typesEvolutionary correlationPhylogenetic evidenceEvolutionary changeDermal skin fibroblastsMammalian speciesExpression profilesPlacental invasivenessComparative datasetCancer growthCultured skin fibroblastsStromal fibroblastsFibroblastsMouse strainsFibroblast activation protein: Pivoting cancer/chemotherapeutic insight towards heart failure
Gehris J, Ervin C, Hawkins C, Womack S, Churillo A, Doyle J, Sinusas A, Spinale F. Fibroblast activation protein: Pivoting cancer/chemotherapeutic insight towards heart failure. Biochemical Pharmacology 2023, 219: 115914. PMID: 37956895, PMCID: PMC10824141, DOI: 10.1016/j.bcp.2023.115914.Peer-Reviewed Original ResearchConceptsFibroblast activation proteinExtracellular matrixCancer progressionFibroblast subtypesProtein signaturesECM structureEnzyme pathwaysActivation proteinTherapeutic targetImportant mechanismFibroblastsProliferationFibroblast growthProteinProgressionPathwayRemodelingFunctionCancerDiscoveryChemotherapeuticsThe tumor microenvironment in hepatocarcinoma: dissecting the functions of cancer-associated fibroblasts
Cadamuro M, Nuozzi G, Simioni P, Fabris L. The tumor microenvironment in hepatocarcinoma: dissecting the functions of cancer-associated fibroblasts. Hepatoma Research 2023, 9: null-null. DOI: 10.20517/2394-5079.2023.94.Peer-Reviewed Original ResearchCancer-associated fibroblastsHepatocellular carcinomaTumor microenvironmentCommon primary liver malignancyFibro-inflammatory conditionPrimary liver malignancyLimited effective treatmentsWorrisome diseaseLiver malignanciesAggressive tumorsEffective treatmentAggressive phenotypeNeoplastic diseaseCell originCirrhotic backgroundEpithelial compartmentTranslational valueSpecific populationsNeoplastic transformationTumorsDiseasePossible ameliorationCell typesRecent findingsFibroblastsSRC and TKS5 mediated podosome formation in fibroblasts promotes extracellular matrix invasion and pulmonary fibrosis
Barbayianni I, Kanellopoulou P, Fanidis D, Nastos D, Ntouskou E, Galaris A, Harokopos V, Hatzis P, Tsitoura E, Homer R, Kaminski N, Antoniou K, Crestani B, Tzouvelekis A, Aidinis V. SRC and TKS5 mediated podosome formation in fibroblasts promotes extracellular matrix invasion and pulmonary fibrosis. Nature Communications 2023, 14: 5882. PMID: 37735172, PMCID: PMC10514346, DOI: 10.1038/s41467-023-41614-x.Peer-Reviewed Original ResearchConceptsPulmonary fibrosisExtracellular matrix invasionLung fibroblastsIdiopathic pulmonary fibrosis patientsIdiopathic pulmonary fibrosisPulmonary fibrosis patientsMatrix invasionPromising therapeutic optionProfibrotic milieuTherapeutic optionsLung tissuePathogenic hallmarkPharmacological targetingFibrosisFibrosis patientsIncurable diseaseEx vivoBleomycinExtracellular matrix componentsTks5 expressionAberrant depositionInvasionMiceFibroblastsSrc kinaseFibroblasts – the cellular choreographers of wound healing
Knoedler S, Broichhausen S, Guo R, Dai R, Knoedler L, Kauke-Navarro M, Diatta F, Pomahac B, Machens H, Jiang D, Rinkevich Y. Fibroblasts – the cellular choreographers of wound healing. Frontiers In Immunology 2023, 14: 1233800. PMID: 37646029, PMCID: PMC10461395, DOI: 10.3389/fimmu.2023.1233800.Peer-Reviewed Original ResearchConceptsFibroblast diversityInnate immune cellsNovel treatment modalitiesWound healing functionsFascial connective tissueRole of fibroblastsTreatment modalitiesImmune cellsWound repairScar tissueDiversityFibroblastsConnective tissueHealing processWound healingComprehensive understandingMachineryTissueHealing functionCascadeOrgan function is preserved despite reorganization of niche architecture in the hair follicle
Wei H, Du S, Parksong J, Pasolli H, Matte-Martone C, Regot S, Gonzalez L, Xin T, Greco V. Organ function is preserved despite reorganization of niche architecture in the hair follicle. Cell Stem Cell 2023, 30: 962-972.e6. PMID: 37419106, PMCID: PMC10362479, DOI: 10.1016/j.stem.2023.06.003.Peer-Reviewed Original ResearchConceptsNiche architectureDermal papilla fibroblastsDifferentiated lineagesHair follicle growthStereotypic architectureMultipotent progenitorsEpithelial progenitorsFunctional importanceNicheStem cellsFibroblast nicheProgenitorsPowerful modelIntravital imagingDermal papillaFibroblastsHair folliclesFollicle growthOrgan functionLineagesDifferentiationCrosstalkHairProliferationCellsContributions of circadian clock genes to cell survival in fibroblast models of lithium-responsive bipolar disorder
Mishra H, Wei H, Rohr K, Ko I, Nievergelt C, Maihofer A, Shilling P, Alda M, Berrettini W, Brennand K, Calabrese J, Coryell W, Frye M, Gage F, Gershon E, McInnis M, Nurnberger J, Oedegaard K, Zandi P, Kelsoe J, McCarthy M. Contributions of circadian clock genes to cell survival in fibroblast models of lithium-responsive bipolar disorder. European Neuropsychopharmacology 2023, 74: 1-14. PMID: 37126998, PMCID: PMC11801370, DOI: 10.1016/j.euroneuro.2023.04.009.Peer-Reviewed Original ResearchConceptsCell survival genesCircadian clockSurvival genesCell survivalCircadian clock genesCircadian rhythmGenetic variationClock genesKnockdown studiesCaspase activityCell deathMolecular pathwaysPrimary fibroblastsCellular modelGenesMouse fibroblastsFibroblast modelApoptosisStaurosporinePER1FibroblastsOpposite mannerLithium responsivenessDistinct patternsClockEfficient reconstruction of cell lineage trees for cell ancestry and cancer
Jang Y, Fasching L, Bae T, Tomasini L, Schreiner J, Szekely A, Fernandez T, Leckman J, Vaccarino F, Abyzov A. Efficient reconstruction of cell lineage trees for cell ancestry and cancer. Nucleic Acids Research 2023, 51: e57-e57. PMID: 37026484, PMCID: PMC10250207, DOI: 10.1093/nar/gkad254.Peer-Reviewed Original ResearchConceptsLineage treesCell ancestryCell lineage treesFirst cell divisionStem cell linesPluripotent stem cell lineLineage reconstructionInduced pluripotent stem cell lineCell divisionCancer progressionLineage representationCell linesMosaic mutationsHuman skin fibroblastsTreesMutationsAncestrySkin fibroblastsMultiple cellsGenomeLineagesZygotesLinesFibroblastsCellsOptimized protocol for direct cardiac reprogramming in mice using Ascl1 and Mef2c
Wang H, Keepers B, Liu J, Qian L. Optimized protocol for direct cardiac reprogramming in mice using Ascl1 and Mef2c. STAR Protocols 2023, 4: 102204. PMID: 36989109, PMCID: PMC10074248, DOI: 10.1016/j.xpro.2023.102204.Peer-Reviewed Original ResearchCardiac reprogrammingNeonatal mouse cardiac fibroblastsIntermediate progenitor stageDirect cardiac reprogrammingCardiomyocyte-like cellsMouse cardiac fibroblastsConversion of fibroblastsCalcium fluxReprogramming factorsProgenitor stageCardiac fibroblastsSarcomere structureAscl1MEF2CReprogrammingMiceGene expressionFibroblastsOptimized protocolSynaptic vesicle proteins and ATG9A self-organize in distinct vesicle phases within synapsin condensates
Park D, Wu Y, Wang X, Gowrishankar S, Baublis A, De Camilli P. Synaptic vesicle proteins and ATG9A self-organize in distinct vesicle phases within synapsin condensates. Nature Communications 2023, 14: 455. PMID: 36709207, PMCID: PMC9884207, DOI: 10.1038/s41467-023-36081-3.Peer-Reviewed Original ResearchConceptsMembrane proteinsSV membrane proteinsVesicle membrane proteinEctopic expression systemSynaptic vesicle proteinsSynaptic vesicle clustersSV proteinsVesicle proteinsEctopic expressionExpression systemVesicle clustersSynapsinProteinLiquid-like propertiesVesiclesDistinct classesDual roleSynapsin 1FibroblastsATG9ASynapsesExpressionDistinct phasesNerve terminalsClusters
2022
Dysregulation of TSP2-Rac1-WAVE2 axis in diabetic cells leads to cytoskeletal disorganization, increased cell stiffness, and dysfunction
Xing H, Huang Y, Kunkemoeller B, Dahl P, Muraleetharan O, Malvankar N, Murrell M, Kyriakides T. Dysregulation of TSP2-Rac1-WAVE2 axis in diabetic cells leads to cytoskeletal disorganization, increased cell stiffness, and dysfunction. Scientific Reports 2022, 12: 22474. PMID: 36577792, PMCID: PMC9797577, DOI: 10.1038/s41598-022-26337-1.Peer-Reviewed Original ResearchConceptsCell-derived matricesCell stiffnessFamily verprolin-homologous protein 2Active Rac1Thrombospondin-2Homologous protein 2Less traction forceCytoskeleton organizationExtracellular matrix productionMajor cell populationF-actinCytoskeletal disorganizationRegulatory roleProtein 2Matrix productionCritical functionsECM productionArt microscopy techniquesNew functionsCell populationsSpindle-like shapeRac1Normal fibroblastsFibroblastsWound space
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