2024
Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease
Yang M, Lee S, Neely J, Hinchcliff M, Wolters P, Sirota M. Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease. Frontiers In Immunology 2024, 15: 1326922. PMID: 38348044, PMCID: PMC10859856, DOI: 10.3389/fimmu.2024.1326922.Peer-Reviewed Original ResearchConceptsScleroderma-associated interstitial lung diseaseSSc-ILDInterstitial lung diseaseLung tissueGene expression meta-analysisPulmonary fibrosisLung diseaseSenescence signatureDegree of skin involvementIdiopathic pulmonary fibrosisTelomere lengthType II alveolar cellsCellular senescence signaturesCellular senescenceIndependent of ageSkin involvementSSc skinExpression meta-analysisHealthy controlsAssociated with degreeAlveolar cellsLungMeta-analysisAging genesFibrosis
2019
Single-Cell Transcriptomic Analysis of Human Lung Provides Insights into the Pathobiology of Pulmonary Fibrosis
Reyfman PA, Walter JM, Joshi N, Anekalla KR, McQuattie-Pimentel AC, Chiu S, Fernandez R, Akbarpour M, Chen CI, Ren Z, Verma R, Abdala-Valencia H, Nam K, Chi M, Han S, Gonzalez-Gonzalez FJ, Soberanes S, Watanabe S, Williams KJN, Flozak AS, Nicholson TT, Morgan VK, Winter DR, Hinchcliff M, Hrusch CL, Guzy RD, Bonham CA, Sperling AI, Bag R, Hamanaka RB, Mutlu GM, Yeldandi AV, Marshall SA, Shilatifard A, Amaral LAN, Perlman H, Sznajder JI, Argento AC, Gillespie CT, Dematte J, Jain M, Singer BD, Ridge KM, Lam AP, Bharat A, Bhorade SM, Gottardi CJ, Budinger GRS, Misharin AV. Single-Cell Transcriptomic Analysis of Human Lung Provides Insights into the Pathobiology of Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2019, 199: 1517-1536. PMID: 30554520, PMCID: PMC6580683, DOI: 10.1164/rccm.201712-2410oc.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingRNA sequencingPulmonary fibrosisAlveolar macrophagesLung tissueSingle-cell transcriptomic analysisEpithelial cellsCell populationsNext-generation sequencing technologiesSingle-cell atlasHuman lungDiverse cell populationsExpression of genesRare cell populationsPulmonary fibrosis pathogenesisIdiopathic pulmonary fibrosisAirway stem cellsIndividual cell populationsTranscriptomic analysisSequencing technologiesWnt secretionRNA hybridizationSenescent cellsTransplant donorsDiscovery-based approachIncreased monocyte count as a cellular biomarker for poor outcomes in fibrotic diseases: a retrospective, multicentre cohort study
Scott MKD, Quinn K, Li Q, Carroll R, Warsinske H, Vallania F, Chen S, Carns MA, Aren K, Sun J, Koloms K, Lee J, Baral J, Kropski J, Zhao H, Herzog E, Martinez FJ, Moore BB, Hinchcliff M, Denny J, Kaminski N, Herazo-Maya JD, Shah NH, Khatri P. Increased monocyte count as a cellular biomarker for poor outcomes in fibrotic diseases: a retrospective, multicentre cohort study. The Lancet Respiratory Medicine 2019, 7: 497-508. PMID: 30935881, PMCID: PMC6529612, DOI: 10.1016/s2213-2600(18)30508-3.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisAbsolute monocyte countMonocyte countImmune cell typesElectronic health recordsPoor outcomeHigh riskSystemic sclerosisMonocyte percentageHypertrophic cardiomyopathyHigh absolute monocyte countPeripheral blood mononuclear cell samplesComplete blood count valuesSpecific immune cell typesTransplant-free survivalMulticentre cohort studyHealth recordsHigh-risk patientsBlood count valuesSame clinical presentationHigher monocyte countMononuclear cell samplesRisk of mortalityCell types
2017
A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis
Taroni JN, Greene CS, Martyanov V, Wood TA, Christmann RB, Farber HW, Lafyatis RA, Denton CP, Hinchcliff ME, Pioli PA, Mahoney JM, Whitfield ML. A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis. Genome Medicine 2017, 9: 27. PMID: 28330499, PMCID: PMC5363043, DOI: 10.1186/s13073-017-0417-1.Peer-Reviewed Original ResearchConceptsDisease-associated signaturesFunctional genomic networksGene expression signaturesPulmonary fibrosisAutoimmune diseasesDisease processMulti-organ autoimmune diseaseDistinct underlying pathologyPro-fibrotic macrophagesInternal organ involvementPulmonary arterial hypertensionExpression signaturesSkin of patientsInnate immune systemWilcoxon rank sum testGenomic networksRank sum testBackgroundSystemic sclerosisArterial hypertensionOrgan involvementSystemic sclerosisUnderlying pathologyLung microenvironmentSkin fibrosisFibrotic genes
2011
Canonical Wnt signaling induces skin fibrosis and subcutaneous lipoatrophy: A novel mouse model for scleroderma?
Wei J, Melichian D, Komura K, Hinchcliff M, Lam AP, Lafyatis R, Gottardi CJ, MacDougald OA, Varga J. Canonical Wnt signaling induces skin fibrosis and subcutaneous lipoatrophy: A novel mouse model for scleroderma? Arthritis & Rheumatism 2011, 63: 1707-1717. PMID: 21370225, PMCID: PMC3124699, DOI: 10.1002/art.30312.Peer-Reviewed Original ResearchConceptsSystemic sclerosisSubcutaneous adipose tissueTransgenic miceWnt-10bBiopsy specimensDermal fibrosisMouse modelAdipose tissueLesional skin biopsy specimensSkin biopsy specimensNovel mouse modelMesenchymal cellsSmooth muscle actin gene expressionSkin fibroblastsNovel animal modelFibrotic gene expressionWnt/β-catenin signalingSetting of fibrosisGrowth factor βΒ-catenin signalingPulmonary fibrosisSubcutaneous lipoatrophySkin fibrosisGene expressionMyofibroblast accumulation