Featured Publications
SARS-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 cellsInfectionDecellularization compromises mechanical and structural properties of the native trachea
Greaney A, Ramachandra A, Yuan Y, Korneva A, Humphrey J, Niklason L. Decellularization compromises mechanical and structural properties of the native trachea. Biomaterials And Biosystems 2023, 9: 100074. PMID: 36967724, PMCID: PMC10036236, DOI: 10.1016/j.bbiosy.2023.100074.Peer-Reviewed Original ResearchMechanical behaviorGraft failureNative tracheaMechanical failureTissue engineering technologyDepletion of proteoglycansAirway narrowingAirway replacementClinical interventionsWestern blotTracheaMajor causeTracheal graftsEngineering technologyHistological stainingTracheal replacementDifferent decellularization protocolsSignificant differencesClinical implantationTissue repairCollagen IStructural deteriorationStructural propertiesDecellularization protocolGreat potentialThe History of Engineered Tracheal Replacements: Interpreting the Past and Guiding the Future
Greaney A, Niklason L. The History of Engineered Tracheal Replacements: Interpreting the Past and Guiding the Future. Tissue Engineering Part B Reviews 2020, 27: 341-352. PMID: 33045942, PMCID: PMC8390779, DOI: 10.1089/ten.teb.2020.0238.Peer-Reviewed Original ResearchConceptsFailure modesTracheal graftsTracheal replacementGraft mechanicsDesign criteriaInert materialLong segment defectType of graftRecent preclinical workClinical care prioritiesRigid tubeLeuven protocolTracheal allograftsClinical followAirway reconstructionCadaveric allograftsCircumferential defectsTissue analysis techniquesEngineersPreclinical workReplacement graftsCare prioritiesGraft performanceHuman patientsGraftPlatform 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
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 Research
2022
Computation 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 ResearchExpression of the transcription factor PU.1 induces the generation of microglia-like cells in human cortical organoids
Cakir B, Tanaka Y, Kiral FR, Xiang Y, Dagliyan O, Wang J, Lee M, Greaney AM, Yang WS, duBoulay C, Kural MH, Patterson B, Zhong M, Kim J, Bai Y, Min W, Niklason LE, Patra P, Park IH. Expression of the transcription factor PU.1 induces the generation of microglia-like cells in human cortical organoids. Nature Communications 2022, 13: 430. PMID: 35058453, PMCID: PMC8776770, DOI: 10.1038/s41467-022-28043-y.Peer-Reviewed Original ResearchConceptsHuman embryonic stem cellsHuman cortical organoidsTranscription factor PUSingle-cell RNA sequencingMicroglia-like cellsSingle-cell transcriptomicsEmbryonic stem cellsDisease stage IIIRole of microgliaAD-associated genesExpression of genesCortical organoidsNeurodegenerative disordersRNA sequencingMolecular damageIntact complementStem cellsDysfunction of microgliaFunctional microgliaReduced expressionGenesCell clustersExpressionChemokine systemHuman microglia
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 ResearchAn ex vivo physiologic and hyperplastic vessel culture model to study intra-arterial stent therapies
Wang J, Kural MH, Wu J, Leiby KL, Mishra V, Lysyy T, Li G, Luo J, Greaney A, Tellides G, Qyang Y, Huang N, Niklason LE. An ex vivo physiologic and hyperplastic vessel culture model to study intra-arterial stent therapies. Biomaterials 2021, 275: 120911. PMID: 34087584, PMCID: PMC9195126, DOI: 10.1016/j.biomaterials.2021.120911.Peer-Reviewed Original ResearchSingle-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes
Ravindra NG, Alfajaro MM, Gasque V, Huston NC, Wan H, Szigeti-Buck K, Yasumoto Y, Greaney AM, Habet V, Chow RD, Chen JS, Wei J, Filler RB, Wang B, Wang G, Niklason LE, Montgomery RR, Eisenbarth SC, Chen S, Williams A, Iwasaki A, Horvath TL, Foxman EF, Pierce RW, Pyle AM, van Dijk D, Wilen CB. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLOS Biology 2021, 19: e3001143. PMID: 33730024, PMCID: PMC8007021, DOI: 10.1371/journal.pbio.3001143.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Human bronchial epithelial cellsInterferon-stimulated genesCell state changesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCell tropismCoronavirus 2 infectionCoronavirus disease 2019Onset of infectionCell-intrinsic expressionCourse of infectionAir-liquid interface culturesHost-viral interactionsBronchial epithelial cellsSingle-cell RNA sequencingCell typesIL-1Disease 2019Human airwaysDevelopment of therapeuticsDrug AdministrationViral replication
2020
Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Disease 2019
Wagner D, Ikonomou L, Gilpin S, Magin C, Cruz F, Greaney A, Magnusson M, Chen Y, Davis B, Vanuytsel K, Enes S, Krasnodembskaya A, Lehmann M, Westergren-Thorsson G, Stegmayr J, Alsafadi H, Hoffman E, Weiss D, Ryan A. Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Disease 2019. ERJ Open Research 2020, 6: 00123-2020. PMID: 33123557, PMCID: PMC7569162, DOI: 10.1183/23120541.00123-2020.Peer-Reviewed Original ResearchCell therapyProgenitor cellsLung stemLung biologyInduced pluripotent stem cell modelsInternational Society for CellTreatment of lung diseasesPluripotent stem cell modelsPulmonary Fibrosis FoundationCystic Fibrosis FoundationStem cell modelRegenerative medicine productsAlpha-1 FoundationUniversity of Vermont Larner College of MedicineGene therapyCystic fibrosisLung diseaseCollege of MedicineTherapyStem cellsAlpha 1LungBlood InstituteNational HeartExtracellular vesicles
2019
Single-cell connectomic analysis of adult mammalian lungs
Raredon MSB, Adams TS, Suhail Y, Schupp JC, Poli S, Neumark N, Leiby KL, Greaney AM, Yuan Y, Horien C, Linderman G, Engler AJ, Boffa DJ, Kluger Y, Rosas IO, Levchenko A, Kaminski N, Niklason LE. Single-cell connectomic analysis of adult mammalian lungs. Science Advances 2019, 5: eaaw3851. PMID: 31840053, PMCID: PMC6892628, DOI: 10.1126/sciadv.aaw3851.Peer-Reviewed Original ResearchConceptsTissue homeostasisMammalian lungSingle-cell RNA sequencing techniquesAdult mammalian lungRNA sequencing techniquesCell-cell interactionsSequencing techniquesKey pathwaysAlveolar type IFunctional roleCell typesCell populationsRegenerative medicineHomeostatic mechanismsHomeostasisFine architectureFunctional lung tissueIncomplete understandingMajor roleType ITissueRegulationPathwayAlveolar cell populationsDistal lung
2018
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Greaney A, Choi J, Beely B, Gubbins E, Ghaedi M, Wendorff D, Roberts T, Le A, Batchinsky A, Niklason L. 1122. Critical Care Medicine 2018, 46: 544. DOI: 10.1097/01.ccm.0000529127.88144.3a.Peer-Reviewed Original Research
2016
Engineered Tissue–Stent Biocomposites as Tracheal Replacements
Zhao L, Sundaram S, Le AV, Huang AH, Zhang J, Hatachi G, Beloiartsev A, Caty MG, Yi T, Leiby K, Gard A, Kural MH, Gui L, Rocco KA, Sivarapatna A, Calle E, Greaney A, Urbani L, Maghsoudlou P, Burns A, DeCoppi P, Niklason LE. Engineered Tissue–Stent Biocomposites as Tracheal Replacements. Tissue Engineering Part A 2016, 22: 1086-1097. PMID: 27520928, PMCID: PMC5312617, DOI: 10.1089/ten.tea.2016.0132.Peer-Reviewed Original ResearchElastic, silk‐cardiac extracellular matrix hydrogels exhibit time‐dependent stiffening that modulates cardiac fibroblast response
Stoppel W, Gao A, Greaney A, Partlow B, Bretherton R, Kaplan D, Black L. Elastic, silk‐cardiac extracellular matrix hydrogels exhibit time‐dependent stiffening that modulates cardiac fibroblast response. Journal Of Biomedical Materials Research Part A 2016, 104: 3058-3072. PMID: 27480328, PMCID: PMC5805141, DOI: 10.1002/jbm.a.35850.Peer-Reviewed Original ResearchConceptsExtracellular matrix hydrogelTissue-derived extracellular matrixEndothelial cell ingrowthSilk hydrogelsMechanical propertiesCell ingrowthWeeks in vivoHydrogel stiffeningMatrix hydrogelHydrogelsFunctional cardiac repairStiffeningFocal adhesion proteinsCardiac fibroblastsExpression of integrinsCardiac repairHeart failureProgression to heart failureTissue in vitroAdhesion proteinsCell growthExtracellular matrix