2025
Buprenorphine induces human fetal membrane sterile inflammation
Lynn T, Kelleher M, Georges H, McCauley E, Logan R, Yonkers K, Abrahams V. Buprenorphine induces human fetal membrane sterile inflammation. Journal Of Reproductive Immunology 2025, 168: 104445. PMID: 39914058, PMCID: PMC11890952, DOI: 10.1016/j.jri.2025.104445.Peer-Reviewed Original ResearchConceptsOpioid-use disorderPreterm birthToll-like receptor 4Prostaglandin E2Sterile inflammationRate of preterm birthAssociated with pregnancy complicationsInnate immune toll-like receptor 4Maternal-fetal interfaceNeutrophil chemokine IL-8Induce sterile inflammationM-opioid receptorCytokines IL-1bInflammatory cytokines IL-6Chemokine IL-8Cytokines IL-6Maternal morbidityPregnancy complicationsOpioid useOpioid-usersHuman FMInflammatory profileMembrane weakeningIL-1BPreterm
2024
Human induced pluripotent stem cell-derived cardiomyocytes to study inflammation-induced aberrant calcium transient
Tatekoshi Y, Chen C, Shapiro J, Chang H, Blancard M, Lyra-Leite D, Burridge P, Feinstein M, D'Aquila R, Hsue P, Ardehali H. Human induced pluripotent stem cell-derived cardiomyocytes to study inflammation-induced aberrant calcium transient. ELife 2024, 13: rp95867. PMID: 39331464, PMCID: PMC11434618, DOI: 10.7554/elife.95867.Peer-Reviewed Original ResearchMeSH KeywordsCalciumCells, CulturedCytokinesHeart FailureHIV InfectionsHumansInduced Pluripotent Stem CellsInflammationMyocytes, CardiacConceptsHuman induced pluripotent stem cell-derived cardiomyocytesPluripotent stem cell-derived cardiomyocytesStem cell-derived cardiomyocytesCell-derived cardiomyocytesUptake in vitroHIV viremiaDiastolic dysfunctionHIV patientsCardiomyocyte relaxationSarcoplasmic reticulumSGLT2 inhibitorsHeart failurePotential new interventionsInflammatory cytokinesAnimal modelsHFpEFStudy molecular mechanismsMito-TEMPOCardiomyocytesCytokinesHIVPatientsRelaxation defectsPLWHSerumTert-expressing cells contribute to salivary gland homeostasis and tissue regeneration after radiation therapy
Guan L, Viswanathan V, Jiang Y, Vijayakumar S, Cao H, Zhao J, Colburg D, Neuhöfer P, Zhang Y, Wang J, Xu Y, Laseinde E, Hildebrand R, Rahman M, Frock R, Kong C, Beachy P, Artandi S, Le Q. Tert-expressing cells contribute to salivary gland homeostasis and tissue regeneration after radiation therapy. Genes & Development 2024, 38: 569-582. PMID: 38997156, PMCID: PMC11293384, DOI: 10.1101/gad.351577.124.Peer-Reviewed Original ResearchConceptsSubmandibular glandSalivary gland homeostasisProgenitor cellsGland homeostasisResponse to radiotherapyAdult submandibular glandCell survivalSalivary gland regenerationSelf-renewal capacityEnhanced proliferative activityRadiation therapyDuctal regionsRadiotherapyModulate cell survivalTelomerase-expressingGland regenerationProliferative activityMouse strainsTERT expressionCreERT2 recombinaseSalivary gland biologyRadiation exposureTERT locusIn vitro cultureCell populationsHuman regulatory memory B cells defined by expression of TIM-1 and TIGIT are dysfunctional in multiple sclerosis
Varghese J, Kaskow B, von Glehn F, Case J, Li Z, Julé A, Berdan E, Sui S, Hu Y, Krishnan R, Chitnis T, Kuchroo V, Weiner H, Baecher-Allan C. Human regulatory memory B cells defined by expression of TIM-1 and TIGIT are dysfunctional in multiple sclerosis. Frontiers In Immunology 2024, 15: 1360219. PMID: 38745667, PMCID: PMC11091236, DOI: 10.3389/fimmu.2024.1360219.Peer-Reviewed Original ResearchConceptsMemory B cell subsetsMemory B cellsB cell subsetsT cell activationB cellsT cellsMultiple sclerosisIL-17ATIM-1Levels of CD4+ T cell activationAllogeneic CD4+ T cellsRelapsing-remittingAssociated with response to therapyAnti-CD20 treated patientsCD4+ T cell activationDouble positive (DPCD4+ T cellsExpression of TIM-1Genes associated with T-cell activationInduction of inflammatory markersInduce T cell proliferationHuman memory B cellsLack of cell surface markersRegulatory B cellsExpression of genes associated with T-cell activationTRPM7 facilitates fibroblast-like synoviocyte proliferation, metastasis and inflammation through increasing IL-6 stability via the PKCα-HuR axis in rheumatoid arthritis
Lin Y, Chen Y, Hu W, Liu X, Hao W, Xing J, Ding J, Xu Y, Yao F, Zhao Y, Wang K, Li S, Yu Q, Hu W, Zhou R. TRPM7 facilitates fibroblast-like synoviocyte proliferation, metastasis and inflammation through increasing IL-6 stability via the PKCα-HuR axis in rheumatoid arthritis. International Immunopharmacology 2024, 132: 111933. PMID: 38581988, DOI: 10.1016/j.intimp.2024.111933.Peer-Reviewed Original ResearchConceptsTransient receptor potential melastatin 7Rheumatoid arthritisInhibition of transient receptor potential melastatin 7Human RA patientsSynovial hyperplasiaAdjuvant-induced arthritis ratsIncreased TRPM7 expressionIL-6 mRNATreatment of RAPathogenesis of RAFibroblast-like synoviocytesTRPM7 silencingProgression of rheumatoid arthritisTRPM7 expressionChannel inhibitionCation channelsRA patientsMetastasisPharmacological inhibitionArthritis ratsInflammationNuclear translocationSynoviocyte proliferationHyperplasiaProliferationStromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy
Liu X, Li B, Wang S, Zhang E, Schultz M, Touma M, Da Rocha A, Evans S, Eichmann A, Herron T, Chen R, Xiong D, Jaworski A, Weiss S, Si M. Stromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy. Circulation Research 2024, 134: 913-930. PMID: 38414132, PMCID: PMC10977056, DOI: 10.1161/circresaha.122.321292.Peer-Reviewed Original ResearchConceptsTransverse aortic constrictionAortic constrictionPressure overloadCardiomyocyte hypertrophyVascular mural cellsCardiomyocyte hypertrophy in vitroDecreased left ventricular hypertrophyStimulate cardiomyocyte hypertrophyCongenital heart defectsCell-specific knockoutLeft ventricular functionAdverse cardiac remodelingVentricular pressure overloadCardiomyocyte-specific deletionMural cellsHypertrophy in vitroPressure overload stressCardiac stromal cellsMyocardial tissue samplesEffects in vitroIn vitro studiesHypertrophy-related genesHeart defectsRegulate cardiac developmentVentricular functionExtracellular CIRP induces abnormal activation of fibroblast-like synoviocytes from patients with RA via the TLR4-mediated HDAC3 pathways
Yao F, Zhao Y, Yu Q, Hu W, Lin Y, Chen Y, Li L, Sun C, Li S, Wang K, Yang M, Zhou R, Hu W. Extracellular CIRP induces abnormal activation of fibroblast-like synoviocytes from patients with RA via the TLR4-mediated HDAC3 pathways. International Immunopharmacology 2024, 128: 111525. PMID: 38218010, DOI: 10.1016/j.intimp.2024.111525.Peer-Reviewed Original ResearchConceptsExtracellular cold-inducible RNA-binding proteinCold-inducible RNA-binding proteinToll-like receptor 4Histone deacetylase 3Endogenous proinflammatory moleculesRheumatoid arthritisActivity of RA-FLSAA ratsAbnormal activationProinflammatory moleculesEffect of cold-inducible RNA-binding proteinHistone deacetylase 3 knockdownRelease of IL-1bSeverity of arthritisFibroblast-like synoviocytesDevelopment of rheumatoid arthritisRA-FLSActivation of fibroblast-like synoviocytesIL-33Expression of N-cadherinProinflammatory effectsArthritis severityIL-1BInflammatory diseasesReceptor 4Expression of Transcriptional Factors of T Helper Differentiation (T-bet, GATA-3, RORγt, and FOXP3), MIF Receptors (CD44, CD74, CXCR2, 4, 7), and Th1, Th2, and Th17 Cytokines in PBMC from Control Subjects and Rheumatoid Arthritis Patients
Zerpa-Hernández D, García-Chagollán M, Sánchez-Zuno G, García-Arellano S, Hernández-Bello J, Hernández-Palma L, Cerpa-Cruz S, Martinez-Bonilla G, Nicoletti F, Muñoz-Valle J. Expression of Transcriptional Factors of T Helper Differentiation (T-bet, GATA-3, RORγt, and FOXP3), MIF Receptors (CD44, CD74, CXCR2, 4, 7), and Th1, Th2, and Th17 Cytokines in PBMC from Control Subjects and Rheumatoid Arthritis Patients. 2024, 24: 1169-1182. PMID: 37807647, DOI: 10.2174/0115665240260976230925095330.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsMacrophage migration inhibitory factorT CD4+ lymphocytesMIF receptorRA patientsControl subjectsCS groupTh17 cytokinesRheumatoid arthritisElevated levels of pro-inflammatory cytokinesActivity of Foxp3Multiplex bead analysisLevels of pro-inflammatory cytokinesExpression of CXCR7Expression of CD74Expression of GATA3Levels of cytokinesT helper differentiationBlood mononuclear cellsPro-inflammatory cytokinesMigration inhibitory factorDevelopment of rheumatoid arthritisRheumatoid arthritis patientsProfile cytokinesTh17 responses
2023
Transendothelial Migration of Human B Cells: Chemokine versus Antigen.
Wang V, Pober J, Manes T. Transendothelial Migration of Human B Cells: Chemokine versus Antigen. The Journal Of Immunology 2023, 211: 923-931. PMID: 37530585, PMCID: PMC10529164, DOI: 10.4049/jimmunol.2200887.Peer-Reviewed Original ResearchConceptsB cellsLeukocyte cell adhesion moleculeTransendothelial migrationEndothelial cellsCell adhesion moleculeAdhesion moleculesPeripheral blood CD19B cell subsetsMemory B cellsInnate immune propertiesSites of inflammationMicrovascular endothelial cellsHuman microvascular endothelial cellsHuman B cellsBlood CD19Peripheral bloodCell subsetsVenular flowT cellsICAM-1VCAM-1Immune propertiesSyk activationChemokinesExpression of genesScalable production of tissue-like vascularized liver organoids from human PSCs
Harrison S, Siller R, Tanaka Y, Chollet M, de la Morena-Barrio M, Xiang Y, Patterson B, Andersen E, Bravo-Pérez C, Kempf H, Åsrud K, Lunov O, Dejneka A, Mowinckel M, Stavik B, Sandset P, Melum E, Baumgarten S, Bonanini F, Kurek D, Mathapati S, Almaas R, Sharma K, Wilson S, Skottvoll F, Boger I, Bogen I, Nyman T, Wu J, Bezrouk A, Cizkova D, Corral J, Mokry J, Zweigerdt R, Park I, Sullivan G. Scalable production of tissue-like vascularized liver organoids from human PSCs. Experimental & Molecular Medicine 2023, 55: 2005-2024. PMID: 37653039, PMCID: PMC10545717, DOI: 10.1038/s12276-023-01074-1.Peer-Reviewed Original ResearchConceptsExtracellular matrixSingle-cell RNA sequencingBasic developmental biologyEmbryonic liver developmentPost-translational modificationsLiver-like functionsCostly growth factorsOrganoid modelsKey liver functionsCellular diversityCellular repertoireDevelopmental biologyCellular complexityN-glycosylationRNA sequencingDe novo vascularizationNumber of tissuesProtein productionSerum protein productionLiver developmentHuman PSCsDrug toxicity assessmentOrganoidsSmall moleculesGrowth factorSingle‐Cell Transcriptomics of Bone Marrow Stromal Cells in Diversity Outbred Mice: A Model for Population‐Level scRNA‐Seq Studies
Dillard L, Rosenow W, Calabrese G, Mesner L, Al‐Barghouthi B, Abood A, Farber E, Onengut‐Gumuscu S, Tommasini S, Horowitz M, Rosen C, Yao L, Qin L, Farber C. Single‐Cell Transcriptomics of Bone Marrow Stromal Cells in Diversity Outbred Mice: A Model for Population‐Level scRNA‐Seq Studies. Journal Of Bone And Mineral Research 2023, 38: 1350-1363. PMID: 37436066, PMCID: PMC10528806, DOI: 10.1002/jbmr.4882.Peer-Reviewed Original ResearchConceptsGene regulatory networksMesenchymal lineage cellsBone marrow-derived stromal cellsGenome-wide association studiesOsteocyte-like cellsLineage cellsOsteogenic conditionsTranscriptomic profilesSingle-cell RNA-seqCell typesTranscriptomic data setsGenetics of osteoporosisDisease-associated variantsSingle-cell levelMarrow-derived stromal cellsTranscriptomic perspectiveRegulatory networksCausal genesRNA-seqTranscriptomic dataScRNA-seqMesenchymal progenitorsAssociation studiesGenetic studiesLineage precursorsAssay optimization for the objective quantification of human multilineage colony-forming units
Thompson E, Carlino M, Scanlon V, Grimes H, Krause D. Assay optimization for the objective quantification of human multilineage colony-forming units. Experimental Hematology 2023, 124: 36-44.e3. PMID: 37271449, PMCID: PMC10527702, DOI: 10.1016/j.exphem.2023.05.007.Peer-Reviewed Original ResearchConceptsFluorescence-activated cell sortingLineage potentialCommon myeloid progenitorsHigh-throughput microscopyMultilineage colony-forming unitsProportion of coloniesSpecific growth factorsCFU assayColony-forming unit assaysMultipotent progenitorsProgenitor populationsLineage outputSitu immunofluorescenceMegakaryocytic lineageMK cellsMegakaryocytic cellsCell typesMyeloid progenitorsProgenitor cellsCell morphologyCell sortingUnit assaysIL-3Colony typesCulture conditions
2022
Vascular pathobiology of pulmonary hypertension
Gallardo-Vara E, Ntokou A, Dave J, Jovin D, Saddouk F, Greif D. Vascular pathobiology of pulmonary hypertension. The Journal Of Heart And Lung Transplantation 2022, 42: 544-552. PMID: 36604291, PMCID: PMC10121751, DOI: 10.1016/j.healun.2022.12.012.Peer-Reviewed Original ResearchConceptsPulmonary hypertensionCell typesSmooth muscle cell proliferationEndothelial cell dysfunctionMuscle cell proliferationKruppel-like factor 4Extracellular matrix remodelingHypoxia-inducible factorBox proteinBlood pressurePulmonary arteryInflammatory cellsPulmonary vasculatureMain cell typesVascular pathogenesisVasoactive moleculesCell dysfunctionClinical impactVascular pathobiologyPathological remodelingIntercellular crosstalkLethal diseaseMesenchymal transitionMatrix remodelingGrowth factorHuman dermal fibroblast-derived exosomes induce macrophage activation in systemic sclerosis
Bhandari R, Yang H, Kosarek NN, Smith AE, Garlick JA, Hinchcliff M, Whitfield ML, Pioli PA. Human dermal fibroblast-derived exosomes induce macrophage activation in systemic sclerosis. Rheumatology 2022, 62: si114-si124. PMID: 35946522, PMCID: PMC9910573, DOI: 10.1093/rheumatology/keac453.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedExosomesFibroblastsFibrosisHumansInflammationMacrophage ActivationScleroderma, SystemicSkinConceptsFibroblast-derived exosomesSSc patientsMacrophage activationGender-matched control subjectsSSc fibroblastsDonor-derived macrophagesReciprocal activationUpregulated surface expressionMHC class IICo-cultured macrophagesHealthy control fibroblastsExtracellular matrix depositionCell typesSystemic sclerosisHealthy ageIL-10Production of collagenIL-12p40IL-6Control subjectsSkin biopsiesSSc skinTherapeutic targetingClass IIFlow cytometryHigh Fluid Shear Stress Inhibits Cytokine‐Driven Smad2/3 Activation in Vascular Endothelial Cells
Deng H, Schwartz MA. High Fluid Shear Stress Inhibits Cytokine‐Driven Smad2/3 Activation in Vascular Endothelial Cells. Journal Of The American Heart Association 2022, 11: e025337. PMID: 35861829, PMCID: PMC9707828, DOI: 10.1161/jaha.121.025337.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCytokinesEndothelial CellsEpithelial-Mesenchymal TransitionMiceSignal TransductionStress, MechanicalConceptsInflammatory cytokinesSmad2/3 activationEndothelial cellsNuclear translocationInflammatory cytokine treatmentGrowth factor betaVascular endothelial cellsQuantitative polymerase chain reactionSmad2/3 nuclear translocationTarget gene expressionBackground AtherosclerosisInflammatory mediatorsInflammatory pathwaysPolymerase chain reactionResult of inhibitionCytokine treatmentInhibits CytokineFactor betaMesenchymal transitionHigh fluid shear stressCytokinesEndMTGene expressionLaminar fluid shear stressFluid shear stressPostmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling
Argouarch A, Schultz N, Yang A, Jang Y, Garcia K, Cosme C, Corrales C, Nana A, Karydas A, Spina S, Grinberg L, Miller B, Wyss-Coray T, Abyzov A, Goodarzi H, Seeley W, Kao A. Postmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling. Stem Cell Reviews And Reports 2022, 18: 3050-3065. PMID: 35809166, PMCID: PMC9622518, DOI: 10.1007/s12015-022-10416-x.Peer-Reviewed Original ResearchConceptsDivergent gene expression profilesDefective DNA damage repairDisease modelingDNA damage repairGene expression profilesSpecific cell typesCell linesDura mater cellsDermal fibroblastsSomatic mutation signaturesPatient-derived cellsNormal biologyDamage repairExpression profilesSlow growth rateDifferentiation protocolsCell typesFibroblast-like cellsMutation signaturesProtein markersHuman dermal fibroblastsExhibit phenotypicNeurodegenerative diseasesDura materFibroblastsPseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis
Brereton CJ, Yao L, Davies ER, Zhou Y, Vukmirovic M, Bell JA, Wang S, Ridley RA, Dean L, Andriotis OG, Conforti F, Brewitz L, Mohammed S, Wallis T, Tavassoli A, Ewing RM, Alzetani A, Marshall BG, Fletcher SV, Thurner PJ, Fabre A, Kaminski N, Richeldi L, Bhaskar A, Schofield CJ, Loxham M, Davies DE, Wang Y, Jones MG. Pseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis. ELife 2022, 11: e69348. PMID: 35188460, PMCID: PMC8860444, DOI: 10.7554/elife.69348.Peer-Reviewed Original ResearchConceptsHIF pathway activationPathway activationLung fibrosisOxidative stressHuman lung fibrosisOxidative stress scoreFibrillar collagen synthesisHypoxia-inducible factor (HIF) pathway activationExtracellular matrixActive fibrogenesisFibrosisHuman fibrosisFibrosis tissueHIF activationStress scoresVivo studiesCollagen synthesisMesenchymal cellsCritical pathwaysDownstream activationNormal fibroblastsCritical regulatorHIFActivationHuman tissuesSex differences in developmental patterns of neocortical astroglia: A mouse translatome database
Rurak GM, Simard S, Freitas-Andrade M, Lacoste B, Charih F, Van Geel A, Stead J, Woodside B, Green JR, Coppola G, Salmaso N. Sex differences in developmental patterns of neocortical astroglia: A mouse translatome database. Cell Reports 2022, 38: 110310. PMID: 35108542, DOI: 10.1016/j.celrep.2022.110310.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesCells, CulturedFemaleMaleMice, Inbred C57BLNeocortexNeurogenesisNeuronsSex CharacteristicsConceptsGene expression patternsRibosome affinity purificationDevelopmental time pointsAstroglial phenotypeMaintenance of neuronsRNA sequencingAffinity purificationExpression patternsTelencephalic developmentAstroglial cellsSteroid hormone receptorsSex differencesKey playersNeuronal networksHormone receptorsDevelopmental patternsImportant sex differencesPhenotypeDevelopmental sex differencesWindow of vulnerabilityFemale miceHormonal manipulationPostnatal developmentAstrogliaTranslatomeTargeting fibrocytes in autoimmunity
Bucala RJ. Targeting fibrocytes in autoimmunity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2121739119. PMID: 35086933, PMCID: PMC8812540, DOI: 10.1073/pnas.2121739119.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 samples
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