2024
Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.
Zhao A, Unterman A, Abu Hussein N, Sharma P, Nikola F, Flint J, Yan X, Adams T, Justet A, Sumida T, Zhao J, Schupp J, Raredon M, Ahangari F, Deluliis G, Zhang Y, Buendia-Roldan I, Adegunsoye A, Sperling A, Prasse A, Ryu C, Herzog E, Selman M, Pardo A, Kaminski N. Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis. American Journal Of Respiratory And Critical Care Medicine 2024, 210: 1252-1266. PMID: 38924775, PMCID: PMC11568434, DOI: 10.1164/rccm.202401-0078oc.Peer-Reviewed Original ResearchFibrotic hypersensitivity pneumonitisIdiopathic pulmonary fibrosisPeripheral blood mononuclear cellsBronchoalveolar lavage cellsBlood mononuclear cellsClassical monocytesHypersensitivity pneumonitisPulmonary fibrosisT cellsImmune perturbationsLavage cellsMononuclear cellsCD8+ T cellsCytotoxic T cellsInterstitial lung diseaseHypersensitivity pneumonitis patientsCytotoxic CD4Immune aberrationsPneumonic patientsPneumonitisLung diseaseHealthy controlsImmune mechanismsPatient cellsSingle-cell transcriptomicsPredicting lung aging using scRNA-Seq data
Song Q, Singh A, McDonough J, Adams T, Vos R, De Man R, Myers G, Ceulemans L, Vanaudenaerde B, Wuyts W, Yan X, Schupp J, Hagood J, Kaminski N, Bar-Joseph Z. Predicting lung aging using scRNA-Seq data. PLOS Computational Biology 2024, 20: e1012632. PMID: 39700255, PMCID: PMC11741621, DOI: 10.1371/journal.pcbi.1012632.Peer-Reviewed Original ResearchIPF Aberrant Basaloid Cells Have Chromatin Accessibility Features Distinct From Other Lung Epithelial Cells
Adams T, Schupp J, Balayev A, Justet A, Sharma P, Anderson S, Nekola F, Deiuliis G, Yan X, Wuyts W, Vanaudenaerde B, Kaminski N. IPF Aberrant Basaloid Cells Have Chromatin Accessibility Features Distinct From Other Lung Epithelial Cells. 2024, a4898-a4898. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a4898.Peer-Reviewed Original ResearchFibrotic cocktail treated human precision lung slices replicate the cellular diversity of the IPF lung
Justet A, Pineda H, Adams T, Balayev A, Mitash N, Ishizuka M, Kim H, Khoury J, Cala-GarcĂa J, Flint J, Schupp J, Ahangari F, Yan X, Rosas I, Kaminski N, Königshoff M. Fibrotic cocktail treated human precision lung slices replicate the cellular diversity of the IPF lung. Revue Des Maladies Respiratoires 2024, 41: 218. DOI: 10.1016/j.rmr.2024.01.074.Peer-Reviewed Original ResearchCellular repertoireCell typesSingle cell platformsSequence readsCDNA libraryIllumina platformHuman genomeNucleus transcriptomicsCellular diversityIPF lungsPulmonary fibrosisEMT markersAirway epithelial cellsBasaloid cellsCellular populationsEpithelial cellsFibrotic fibroblastsCell platformLung slicesLung cell populationsHuman precision-cut lung slicesCell populationsSenescence markersCellsBasal markersSingle-cell transcriptomic analysis of human pleura reveals stromal heterogeneity and informs in vitro models of mesothelioma
Obacz J, Valer J, Nibhani R, Adams T, Schupp J, Veale N, Lewis-Wade A, Flint J, Hogan J, Aresu G, Coonar A, Peryt A, Biffi G, Kaminski N, Francies H, Rassl D, Garnett M, Rintoul R, Marciniak S. Single-cell transcriptomic analysis of human pleura reveals stromal heterogeneity and informs in vitro models of mesothelioma. European Respiratory Journal 2024, 63: 2300143. PMID: 38212075, PMCID: PMC10809128, DOI: 10.1183/13993003.00143-2023.Peer-Reviewed Original ResearchConceptsSingle-cell transcriptome atlasSingle-cell levelSingle-cell transcriptome analysisTranscriptome dataTranscriptomic atlasTranscriptomic characterisationMesothelial cellsCell atlasDevelopment of targeted therapiesMalignant mesothelial cellsModel of mesotheliomaUniversal fibroblastsIn vitro model
2023
iDESC: identifying differential expression in single-cell RNA sequencing data with multiple subjects
Liu Y, Zhao J, Adams T, Wang N, Schupp J, Wu W, McDonough J, Chupp G, Kaminski N, Wang Z, Yan X. iDESC: identifying differential expression in single-cell RNA sequencing data with multiple subjects. BMC Bioinformatics 2023, 24: 318. PMID: 37608264, PMCID: PMC10463720, DOI: 10.1186/s12859-023-05432-8.Peer-Reviewed Original ResearchmicroRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis
Ahangari F, Price N, Malik S, Chioccioli M, Bärnthaler T, Adams T, Kim J, Pradeep S, Ding S, Cosme C, Rose K, McDonough J, Aurelien N, Ibarra G, Omote N, Schupp J, DeIuliis G, Nunez J, Sharma L, Ryu C, Dela Cruz C, Liu X, Prasse A, Rosas I, Bahal R, Fernandez-Hernando C, Kaminski N. microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis. JCI Insight 2023, 8: e158100. PMID: 36626225, PMCID: PMC9977502, DOI: 10.1172/jci.insight.158100.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisMiR-33MiR-33 levelsSpecific genetic ablationBronchoalveolar lavage cellsNovel therapeutic approachesMitochondrial homeostasisFatty acid metabolismMacrophages protectsBleomycin injuryLavage cellsLung fibrosisHealthy controlsInflammatory responseTherapeutic approachesImmunometabolic responsesCholesterol effluxFibrosisFatal diseasePharmacological inhibitionSterol regulatory element-binding protein (SREBP) genesGenetic ablationMacrophagesEx vivo mouseIncreased expression of CXCL6 in secretory cells drives fibroblast collagen synthesis and is associated with increased mortality in idiopathic pulmonary fibrosis
Bahudhanapati H, Tan J, Apel R, Seeliger B, Schupp J, Li X, Sullivan D, Sembrat J, Rojas M, Tabib T, Valenzi E, Lafyatis R, Mitash N, Pineda R, Jawale C, Peroumal D, Biswas P, Tedrow J, Adams T, Kaminski N, Wuyts W, McDyer J, Gibson K, Alder J, Königshoff M, Zhang Y, Nouraie M, Prasse A, Kass D. Increased expression of CXCL6 in secretory cells drives fibroblast collagen synthesis and is associated with increased mortality in idiopathic pulmonary fibrosis. European Respiratory Journal 2023, 63: 2300088. PMID: 37918852, DOI: 10.1183/13993003.00088-2023.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAirway epithelial cellsBronchoalveolar lavagePulmonary fibrosisEpithelial cellsCollagen synthesisPathogenesis of IPFCohort of patientsIPF lung fibroblastsEffects of chemokinesAir-liquid interface culturesExpression of CXCL6Collagen I levelsIPF mortalityIPF patientsChemokine levelsIPF fibroblastsPoor survivalDistal lungI levelsWhole lungAnimal modelsEctopic localisationPatientsSingle-cell RNA sequencingCorrection: iDESC: identifying differential expression in single-cell RNA sequencing data with multiple subjects
Liu Y, Zhao J, Adams T, Wang N, Schupp J, Wu W, McDonough J, Chupp G, Kaminski N, Wang Z, Yan X. Correction: iDESC: identifying differential expression in single-cell RNA sequencing data with multiple subjects. BMC Bioinformatics 2023, 24: 394. PMID: 37858060, PMCID: PMC10588114, DOI: 10.1186/s12859-023-05523-6.Peer-Reviewed Original Research
2022
Characterization of the COPD alveolar niche using single-cell RNA sequencing
Sauler M, McDonough JE, Adams TS, Kothapalli N, Barnthaler T, Werder RB, Schupp JC, Nouws J, Robertson MJ, Coarfa C, Yang T, Chioccioli M, Omote N, Cosme C, Poli S, Ayaub EA, Chu SG, Jensen KH, Gomez JL, Britto CJ, Raredon MSB, Niklason LE, Wilson AA, Timshel PN, Kaminski N, Rosas IO. Characterization of the COPD alveolar niche using single-cell RNA sequencing. Nature Communications 2022, 13: 494. PMID: 35078977, PMCID: PMC8789871, DOI: 10.1038/s41467-022-28062-9.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingRNA sequencingCell-specific mechanismsChronic obstructive pulmonary diseaseAdvanced chronic obstructive pulmonary diseaseTranscriptomic network analysisSingle-cell RNA sequencing profilesCellular stress toleranceAberrant cellular metabolismStress toleranceRNA sequencing profilesTranscriptional evidenceCellular metabolismAlveolar nicheSequencing profilesHuman alveolar epithelial cellsChemokine signalingAlveolar epithelial type II cellsObstructive pulmonary diseaseSitu hybridizationType II cellsEpithelial type II cellsSequencingCOPD pathobiologyHuman lung tissue samplesAirway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis
Jaeger B, Schupp JC, Plappert L, Terwolbeck O, Artysh N, Kayser G, Engelhard P, Adams TS, Zweigerdt R, Kempf H, Lienenklaus S, Garrels W, Nazarenko I, Jonigk D, Wygrecka M, Klatt D, Schambach A, Kaminski N, Prasse A. Airway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis. Nature Communications 2022, 13: 5637. PMID: 36163190, PMCID: PMC9513076, DOI: 10.1038/s41467-022-33193-0.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAirway basal cellsPulmonary fibrosisNovel mouse xenograft modelEffect of saracatinibBasal cellsLimited treatment optionsMouse xenograft modelLung developmental processesConnectivity Map analysisExtracellular matrix depositionIPF lungsBronchial brushSevere fibrosisTreatment optionsBronchial brushingsNRG miceHealthy volunteersXenograft modelCyst-like structuresProfibrotic changesAlveolar compartmentFatal diseaseFibrosisPotent Src inhibitorCINS: Cell Interaction Network inference from Single cell expression data
Yuan Y, Cosme C, Adams TS, Schupp J, Sakamoto K, Xylourgidis N, Ruffalo M, Li J, Kaminski N, Bar-Joseph Z. CINS: Cell Interaction Network inference from Single cell expression data. PLOS Computational Biology 2022, 18: e1010468. PMID: 36095011, PMCID: PMC9499239, DOI: 10.1371/journal.pcbi.1010468.Peer-Reviewed Original ResearchConceptsCell type interactionsSingle-cell expression dataSingle-cell RNA-seq dataRNA-seq dataScRNA-seq experimentsCell-cell interactionsExpression dataCell typesMouse datasetsNetwork inferenceCell interactionsInteraction predictionNetwork analysisInference pipelineGenesCINSProteinInteractionBayesian network analysisComputation and visualization of cell–cell signaling topologies in single-cell systems data using Connectome
Raredon MSB, Yang J, Garritano J, Wang M, Kushnir D, Schupp JC, Adams TS, Greaney AM, Leiby KL, Kaminski N, Kluger Y, Levchenko A, Niklason LE. Computation and visualization of cell–cell signaling topologies in single-cell systems data using Connectome. Scientific Reports 2022, 12: 4187. PMID: 35264704, PMCID: PMC8906120, DOI: 10.1038/s41598-022-07959-x.Peer-Reviewed Original Research
2021
Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis
Vukmirovic M, Yan X, Gibson KF, Gulati M, Schupp JC, DeIuliis G, Adams TS, Hu B, Mihaljinec A, Woolard TN, Lynn H, Emeagwali N, Herzog EL, Chen ES, Morris A, Leader JK, Zhang Y, Garcia JGN, Maier LA, Collman RG, Drake WP, Becich MJ, Hochheiser H, Wisniewski SR, Benos PV, Moller DR, Prasse A, Koth LL, Kaminski N. Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis. European Respiratory Journal 2021, 58: 2002950. PMID: 34083402, PMCID: PMC9759791, DOI: 10.1183/13993003.02950-2020.Peer-Reviewed Original ResearchConceptsWeighted gene co-expression network analysisGene co-expression network analysisCo-expression network analysisGene expression programsGene expression patternsDistinct transcriptional programsImmune response pathwaysIon Torrent ProtonMicroarray expression datasetsExpression programsTranscriptional programsPhenotypic traitsGene modulesResponse pathwaysRNA sequencingMolecular endotypesExpression patternsGene expressionHilar lymphadenopathyOrgan involvementGenomic researchMechanistic targetExpression datasetsT helper type 1T cell immune responsesIntegrated Single-Cell Atlas of Endothelial Cells of the Human Lung
Schupp JC, Adams TS, Cosme C, Raredon MSB, Yuan Y, Omote N, Poli S, Chioccioli M, Rose KA, Manning EP, Sauler M, DeIuliis G, Ahangari F, Neumark N, Habermann AC, Gutierrez AJ, Bui LT, Lafyatis R, Pierce RW, Meyer KB, Nawijn MC, Teichmann SA, Banovich NE, Kropski JA, Niklason LE, Pe’er D, Yan X, Homer RJ, Rosas IO, Kaminski N. Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung. Circulation 2021, 144: 286-302. PMID: 34030460, PMCID: PMC8300155, DOI: 10.1161/circulationaha.120.052318.Peer-Reviewed Original ResearchConceptsDifferential expression analysisPrimary lung endothelial cellsLung endothelial cellsCell typesMarker genesExpression analysisSingle-cell RNA sequencing dataCross-species analysisVenous endothelial cellsEndothelial marker genesSingle-cell atlasMarker gene setsRNA sequencing dataEndothelial cellsSubsequent differential expression analysisDifferent lung cell typesResident cell typesLung cell typesCellular diversityEndothelial cell typesCapillary endothelial cellsHuman lung endothelial cellsPhenotypic diversityEndothelial diversityIndistinguishable populationsA Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds
Yuan Y, Leiby KL, Greaney AM, Raredon MSB, Qian H, Schupp JC, Engler AJ, Baevova P, Adams TS, Kural MH, Wang J, Obata T, Yoder MC, Kaminski N, Niklason LE. A Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds. Frontiers In Bioengineering And Biotechnology 2021, 9: 760309. PMID: 34869270, PMCID: PMC8640093, DOI: 10.3389/fbioe.2021.760309.Peer-Reviewed Original ResearchVascular diseaseEndothelial phenotypeLung vascular diseaseAcute lung injuryPulmonary microvascular functionWhole lung scaffoldsVascular barrier functionLung injuryMicrovascular functionEndothelial cell coverageSingle-cell RNA-sequencing analysisLPS treatmentProinflammatory signalsWhole lungLung endotheliumLung systemVascular barrierOrgan engineering approachesBarrier functionLungWhole-organ scaffoldsVascular structuresDrug mechanismsEndotheliumDiseaseChronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity
Bui LT, Winters NI, Chung MI, Joseph C, Gutierrez AJ, Habermann AC, Adams TS, Schupp JC, Poli S, Peter LM, Taylor CJ, Blackburn JB, Richmond BW, Nicholson AG, Rassl D, Wallace WA, Rosas IO, Jenkins RG, Kaminski N, Kropski JA, Banovich NE. Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity. Nature Communications 2021, 12: 4314. PMID: 34262047, PMCID: PMC8280215, DOI: 10.1038/s41467-021-24467-0.Peer-Reviewed Original ResearchConceptsChronic lung diseaseLung diseaseImmune responseSARS-CoV-2 entry factorsSevere coronavirus disease-19SARS-CoV-2 infectionWorse COVID-19 outcomesSARS-CoV-2 entryAdaptive immune responsesCoronavirus disease-19COVID-19 outcomesInnate immune responseInflammatory gene expression programSimilar cellular distributionPoor outcomePeripheral lungViral exposureDisease-19Inflammatory microenvironmentEntry factorsLung epitheliumLung cellsViral replicationAT2 cellsBasal differencesSingle-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma
Chen A, Diaz-Soto MP, Sanmamed MF, Adams T, Schupp JC, Gupta A, Britto C, Sauler M, Yan X, Liu Q, Nino G, Cruz CSD, Chupp GL, Gomez JL. Single-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma. Respiratory Research 2021, 22: 122. PMID: 33902571, PMCID: PMC8074196, DOI: 10.1186/s12931-021-01709-9.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsSevere asthmaEffector T cellsBlood mononuclear cellsT cellsHealthy controlsPoly IDendritic cellsMononuclear cellsUnstimulated peripheral blood mononuclear cellsInterferon responseTLR3 agonist poly IImpaired interferon responseMain cell subsetsNatural killer cellsPro-inflammatory profilePro-inflammatory pathwaysC stimulationCyTOF profilingHigh CD8Cell typesEffector cellsKiller cellsCell subsetsMain cell typesLong noncoding RNA TINCR is a novel regulator of human bronchial epithelial cell differentiation state
Omote N, Sakamoto K, Li Q, Schupp JC, Adams T, Ahangari F, Chioccioli M, DeIuliis G, Hashimoto N, Hasegawa Y, Kaminski N. Long noncoding RNA TINCR is a novel regulator of human bronchial epithelial cell differentiation state. Physiological Reports 2021, 9: e14727. PMID: 33527707, PMCID: PMC7851438, DOI: 10.14814/phy2.14727.Peer-Reviewed Original ResearchConceptsTerminal differentiation-induced lncRNANormal human bronchial epithelial cellsTINCR overexpressionCell differentiationNotch genesTissue developmentBronchial epithelial cellsExtracellular matrix organizationCell phenotypeRNA sequencing analysisNumerous biological functionsRole of lncRNAsCell differentiation stateEpithelial cellsHuman bronchial epithelial cellsCiliated cell differentiationStaufen1 proteinNovel regulatorBasal cell phenotypeDownstream regulatorsRNA immunoprecipitationBiological functionsCritical regulatorDifferential expressionDifferentiation state
2020
Gene coexpression networks reveal novel molecular endotypes in alpha-1 antitrypsin deficiency
Chu JH, Zang W, Vukmirovic M, Yan X, Adams T, DeIuliis G, Hu B, Mihaljinec A, Schupp JC, Becich MJ, Hochheiser H, Gibson KF, Chen ES, Morris A, Leader JK, Wisniewski SR, Zhang Y, Sciurba FC, Collman RG, Sandhaus R, Herzog EL, Patterson KC, Sauler M, Strange C, Kaminski N. Gene coexpression networks reveal novel molecular endotypes in alpha-1 antitrypsin deficiency. Thorax 2020, 76: 134-143. PMID: 33303696, PMCID: PMC10794043, DOI: 10.1136/thoraxjnl-2019-214301.Peer-Reviewed Original ResearchConceptsWeighted gene co-expression network analysisAlpha-1 antitrypsin deficiencyGene modulesGene co-expression network analysisDifferential gene expression analysisCo-expression network analysisPeripheral blood mononuclear cellsGene expression patternsPBMC gene expression patternsGene coexpression networksAATD individualsGene expression profilesGene expression analysisBronchoalveolar lavageAugmentation therapyClinical variablesAntitrypsin deficiencyGene expression assaysRNA-seqCoexpression networkGene validationExpression analysisExpression assaysWGCNA modulesExpression patterns
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