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, 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 transcriptomicsSingle-cell RNA-seq analysis of cell-cell communications in human lung reveals a novel role of VEGF-D in acute lung injury
Yuan Y, Sharma L, Tang W, Raredon M, Ahangari F, Khoury J, Wu D, Niklason L, Kaminski N. Single-cell RNA-seq analysis of cell-cell communications in human lung reveals a novel role of VEGF-D in acute lung injury. Physiology 2024, 39: 1314. DOI: 10.1152/physiol.2024.39.s1.1314.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisAcute lung injuryChronic obstructive pulmonary diseaseAcute respiratory distress syndromeAnalysis of cell-cell communicationVEGF-DMicrovascular nicheSingle-cell RNA-seqLung injury modelSingle-cell RNA-seq analysisLung injuryCell-cell communicationLigand-receptor pairsLPS-induced lung injury modelRNA-seqAdjacent cell typesPulmonary diseaseInjury modelHuman lung endothelial cellsBarrier functionImmune cell infiltrationTumor necrosis factor-aRespiratory distress syndromeLung vascular integrityGene expressionVEGF-D Is Enriched in the Human Lung Microvascular Niche and Improves Vascular Integrity During Acute Lung Injury
Yuan Y, Sharma L, Tang W, Raredon M, Ahangari F, Khoury J, Wu D, Niklason L, Kaminski N. VEGF-D Is Enriched in the Human Lung Microvascular Niche and Improves Vascular Integrity During Acute Lung Injury. 2024, a4694-a4694. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a4694.Peer-Reviewed Original ResearchAberrant Alveolar Epithelial Cells Alter the Alveolar Mesenchyme to Promote Fibrosis in a Clinical Sftpc Mutation Model of Lung Fibrosis
Hoffman E, Roque Barboza W, Rodriguez L, Murthy A, Dherwani R, Bennett A, Tomer Y, Raredon M, Beers M, Katzen J. Aberrant Alveolar Epithelial Cells Alter the Alveolar Mesenchyme to Promote Fibrosis in a Clinical Sftpc Mutation Model of Lung Fibrosis. 2024, a5197-a5197. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a5197.Peer-Reviewed Original Research
2023
Rational engineering of lung alveolar epithelium
Leiby K, Yuan Y, Ng R, Raredon M, Adams T, Baevova P, Greaney A, Hirschi K, Campbell S, Kaminski N, Herzog E, Niklason L. Rational engineering of lung alveolar epithelium. Npj Regenerative Medicine 2023, 8: 22. PMID: 37117221, PMCID: PMC10147714, DOI: 10.1038/s41536-023-00295-2.Peer-Reviewed Original ResearchSARS-CoV-2 leverages airway epithelial protective mechanism for viral infection
Greaney A, Raredon M, Kochugaeva M, Niklason L, Levchenko A. SARS-CoV-2 leverages airway epithelial protective mechanism for viral infection. IScience 2023, 26: 106175. PMID: 36788793, PMCID: PMC9912025, DOI: 10.1016/j.isci.2023.106175.Peer-Reviewed Original ResearchSingle-cell RNA sequencing datasetsCell-cell communicationRNA sequencing datasetsViral infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infectionEarly SARS-CoV-2 infectionSequencing datasetsSARS-CoV-2 infectionRepair mechanismsEarly viral entryTissue repair mechanismsMature ciliated cellsAlternative therapeutic approachSARS-CoV-2 virusResponse mechanismsFeedforward loopCell precursorsRapid differentiationViral entryBronchial epitheliumTherapeutic approachesBarrier tissuesKey mechanismCiliated cellsInfection
2022
Comprehensive visualization of cell–cell interactions in single-cell and spatial transcriptomics with NICHES
Raredon M, Yang J, Kothapalli N, Lewis W, Kaminski N, Niklason L, Kluger Y. Comprehensive visualization of cell–cell interactions in single-cell and spatial transcriptomics with NICHES. Bioinformatics 2022, 39: btac775. PMID: 36458905, PMCID: PMC9825783, DOI: 10.1093/bioinformatics/btac775.Peer-Reviewed Original ResearchConceptsCell-cell interactionsCell-cell signalingSingle-cell resolutionSingle-cell dataLocal cellular microenvironmentSingle-cell levelSpatial transcriptomics dataCell clustersExtracellular signalingTranscriptomic dataGene expression valuesSpatial transcriptomicsSignaling mechanismCellular microenvironmentNicheExpression valuesSupplementary dataSignalingTranscriptomicsComprehensive visualizationBioinformaticsInteractionFibroblast inflammatory priming determines regenerative versus fibrotic skin repair in reindeer
Sinha S, Sparks H, Labit E, Robbins H, Gowing K, Jaffer A, Kutluberk E, Arora R, Raredon M, Cao L, Swanson S, Jiang P, Hee O, Pope H, Workentine M, Todkar K, Sharma N, Bharadia S, Chockalingam K, de Almeida L, Adam M, Niklason L, Potter S, Seifert A, Dufour A, Gabriel V, Rosin N, Stewart R, Muench G, McCorkell R, Matyas J, Biernaskie J. Fibroblast inflammatory priming determines regenerative versus fibrotic skin repair in reindeer. Cell 2022, 185: 4717-4736.e25. PMID: 36493752, PMCID: PMC9888357, DOI: 10.1016/j.cell.2022.11.004.Peer-Reviewed Original ResearchConceptsFibrotic scarSite-specific immune responseFull-thickness injurySkin fibroblastsWound healing outcomesInflammatory mediatorsImmunosuppressive phenotypeImmune resolutionLeukocyte recruitmentMyeloid infiltrationImmune responseHuman fetal fibroblastsHealing outcomesFibrotic phenotypeBack skinEctopic transplantationAdult humansSkin woundsScarSkinSkin repairPowerful comparative modelFibroblastsFetal fibroblastsRepairSoluble Signals to Improve Endothelial Integrity in the Lung
Yuan Y, Raredon M, Yuan Q, Obata T, Qian H, Wu D, Kaminski N, Niklason L. Soluble Signals to Improve Endothelial Integrity in the Lung. 2022, a5749-a5749. DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a5749.Peer-Reviewed Original ResearchComputation 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 ResearchCharacterization 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 samplesSingle-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactions
2021
Pressure-Regulated Ventilator Splitting for Disaster Relief: Design, Testing, and Clinical Experience
Raredon MSB, Fisher C, Heerdt PM, Schonberger RB, Nargi A, Nivison S, Fajardo E, Deshpande R, Akhtar S, Greaney AM, Belter J, Raredon T, Zinter J, McKee A, Michalski M, Baevova P, Niklason LE. Pressure-Regulated Ventilator Splitting for Disaster Relief: Design, Testing, and Clinical Experience. Anesthesia & Analgesia 2021, 134: 1094-1105. PMID: 34928890, DOI: 10.1213/ane.0000000000005825.Peer-Reviewed Original ResearchConceptsPositive end-expiratory pressureClinical experienceIndividualized positive end-expiratory pressureIntensive care unitEnd-expiratory pressureCoronavirus disease 2019 (COVID-19) pandemicHealth care teamDisease 2019 pandemicVentilatory supportIll patientsCare unitCare teamVentilator sharingFuture clinical applicationsPatientsIndependent careVentilator capacityClinical applicationCOVID-19 pandemicVentilatorClinical environmentOutline recommendationsMass traumaPandemicHospitalA 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 mechanismsEndotheliumDiseaseMicrovascular fluid flow in ex vivo and engineered lungs
Raredon MSB, Engler AJ, Yuan Y, Greaney AM, Niklason LE. Microvascular fluid flow in ex vivo and engineered lungs. Journal Of Applied Physiology 2021, 131: 1444-1459. PMID: 34554016, PMCID: PMC8616606, DOI: 10.1152/japplphysiol.00286.2020.Peer-Reviewed Original ResearchHigh resolution stereolithography fabrication of perfusable scaffolds to enable long-term meso-scale hepatic culture for disease modeling
Sphabmixay P, Raredon M, Wang A, Lee H, Hammond P, Fang N, Griffith L. High resolution stereolithography fabrication of perfusable scaffolds to enable long-term meso-scale hepatic culture for disease modeling. Biofabrication 2021, 13: 045024. PMID: 34479229, DOI: 10.1088/1758-5090/ac23aa.Peer-Reviewed Original ResearchMechanisms of Hypoxia-Induced Pulmonary Arterial Stiffening in Mice Revealed by a Functional Genetics Assay of Structural, Functional, and Transcriptomic Data
Manning EP, Ramachandra AB, Schupp JC, Cavinato C, Raredon MSB, Bärnthaler T, Cosme C, Singh I, Tellides G, Kaminski N, Humphrey JD. Mechanisms of Hypoxia-Induced Pulmonary Arterial Stiffening in Mice Revealed by a Functional Genetics Assay of Structural, Functional, and Transcriptomic Data. Frontiers In Physiology 2021, 12: 726253. PMID: 34594238, PMCID: PMC8478173, DOI: 10.3389/fphys.2021.726253.Peer-Reviewed Original ResearchPulmonary arteryAdult male C57BL/6J miceElevated pulmonary arterial pressureChronic cardiopulmonary conditionsPulmonary arterial pressureMale C57BL/6J miceElastic pulmonary arteriesArterial pulse wave velocityPulse wave velocityPotential therapeutic targetPulmonary arterial stiffeningSmooth muscle cell phenotypeMuscle cell phenotypeSpecific transcriptomic changesArterial pressureArterial stiffeningHypoxic miceCardiopulmonary conditionsPulmonary circulationC57BL/6J miceSustained hypoxiaTherapeutic targetClinical importanceEndothelial proliferationArteryIntegrated 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 populations
2020
Bioengineering the Blood‐gas Barrier
Leiby KL, Raredon MSB, Niklason LE. Bioengineering the Blood‐gas Barrier. 2020, 10: 415-452. PMID: 32163210, PMCID: PMC7366783, DOI: 10.1002/cphy.c190026.Peer-Reviewed Original ResearchPlatform Effects on Regeneration by Pulmonary Basal Cells as Evaluated by Single-Cell RNA Sequencing
Greaney AM, Adams TS, Raredon M, Gubbins E, Schupp JC, Engler AJ, Ghaedi M, Yuan Y, Kaminski N, Niklason LE. Platform Effects on Regeneration by Pulmonary Basal Cells as Evaluated by Single-Cell RNA Sequencing. Cell Reports 2020, 30: 4250-4265.e6. PMID: 32209482, PMCID: PMC7175071, DOI: 10.1016/j.celrep.2020.03.004.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingBasal marker expressionBasal cellsChronic pulmonary diseaseRat tracheal epitheliumPulmonary diseaseRNA sequencingCell-based therapiesRat tracheaAir-liquid interfaceTissue graftMarker expressionTracheal epitheliumRegenerative outcomesTracheaEpithelial progenitorsDifferential outcomesEpitheliumOutcomesWhole organPopulation level