2025
Modeling SMAD2 Mutations in Induced Pluripotent Stem Cells Provides Insights Into Cardiovascular Disease Pathogenesis.
Ward T, Morton S, Venturini G, Tai W, Jang M, Gorham J, Delaughter D, Wasson L, Khazal Z, Homsy J, Gelb B, Chung W, Bruneau B, Brueckner M, Tristani-Firouzi M, DePalma S, Seidman C, Seidman J. Modeling SMAD2 Mutations in Induced Pluripotent Stem Cells Provides Insights Into Cardiovascular Disease Pathogenesis. Journal Of The American Heart Association 2025, 14: e036860. PMID: 40028843, DOI: 10.1161/jaha.124.036860.Peer-Reviewed Original ResearchConceptsLoss-of-functionCongenital heart diseaseChromatin accessibilityMissense variantsCHD probandsPluripotent stem cellsHomozygous loss-of-functionCHD-associated genesHeterozygous loss-of-functionTranscription factor bindingMutant induced pluripotent stem cellsChromatin immunoprecipitation dataChromatin peaksStem cellsChromatin interactionsInduced pluripotent stem cellsFactor bindingTranscription factor NanogExome sequencingImmunoprecipitation dataTranscription factorsRNA sequencingChromatinMissenseMolecular consequencesKLF2 maintains lineage fidelity and suppresses CD8 T cell exhaustion during acute LCMV infection
Fagerberg E, Attanasio J, Dien C, Singh J, Kessler E, Abdullah L, Shen J, Hunt B, Connolly K, De Brouwer E, He J, Iyer N, Buck J, Borr E, Damo M, Foster G, Giles J, Huang Y, Tsang J, Krishnaswamy S, Cui W, Joshi N. KLF2 maintains lineage fidelity and suppresses CD8 T cell exhaustion during acute LCMV infection. Science 2025, 387: eadn2337. PMID: 39946463, DOI: 10.1126/science.adn2337.Peer-Reviewed Original ResearchConceptsCD8 T cellsT cellsCD8 T cell exhaustionNaive CD8 T cellsAcute LCMV infectionT cell exhaustionT cell fate decisionsLineage fidelityLCMV infectionEffector differentiationAcute infectionExhaustion programTranscription factorsImmune responseEpigenetic modulationSuppress differentiationProgenitor stateKLF2InfectionFunctional stateFate decisionsCD8Translocating gut pathobiont Enterococcus gallinarum induces TH17 and IgG3 anti-RNA–directed autoimmunity in mouse and human
Gronke K, Nguyen M, Fuhrmann H, Santamaria de Souza N, Schumacher J, Pereira M, Löschberger U, Brinkhege A, Becker N, Yang Y, Sonnert N, Leopold S, Martin A, von Münchow-Klein L, Pessoa Rodrigues C, Cansever D, Hallet R, Richter K, Schubert D, Daniel G, Dylus D, Forkel M, Schwinge D, Schramm C, Redanz S, Lassen K, Manfredo Vieira S, Piali L, Palm N, Bieniossek C, Kriegel M. Translocating gut pathobiont Enterococcus gallinarum induces TH17 and IgG3 anti-RNA–directed autoimmunity in mouse and human. Science Translational Medicine 2025, 17: eadj6294. PMID: 39908347, DOI: 10.1126/scitranslmed.adj6294.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusAutoimmune diseasesToll-like receptor 8Gut pathobiontsHuman adaptive immune responseLong-term sequelaeAdaptive immune responsesHuman T cellsChronic autoimmune diseaseHuman monocyte activationContribution to autoimmunityAutoimmune hepatitisAutoantibody titersAnti-<i>E.Autoimmune pathophysiologyLupus modelT-helperLifelong immunosuppressionTargeted therapyT cellsDisease activityLupus erythematosusAutoantibody responseMonocyte activationImmune responsePMA1-containing extracellular vesicles of Candida albicans triggers immune responses and colitis progression
Xu Z, Qiao S, Wang Z, Peng C, Hou Y, Liu B, Cao G, Wang T. PMA1-containing extracellular vesicles of Candida albicans triggers immune responses and colitis progression. Gut Microbes 2025, 17: 2455508. PMID: 39886799, PMCID: PMC11792855, DOI: 10.1080/19490976.2025.2455508.Peer-Reviewed Original ResearchConceptsPMA1 expressionExtracellular vesiclesCell differentiationAdaptor protein CARD9Th17 cell differentiationCARD9 deficiencyActivity of GAPDHVirulence factorsDecreased enzyme activityPma1Immune responseProteomic analysisCARD9Decreased glycolysisIL-17A productionMucosal immune responsesInduce Th17 cell differentiationMesenteric lymph nodesEditing systemAggravated colitisIL-17ALymph nodesColitis progressionAberrant changesGAPDHA CD26+ tendon stem progenitor cell population contributes to tendon repair and heterotopic ossification
Chen S, Lin Y, Yang H, Li Z, Li S, Chen D, Hao W, Zhang S, Chao H, Zhang J, Wang J, Li Z, Li X, Zhan Z, Liu H. A CD26+ tendon stem progenitor cell population contributes to tendon repair and heterotopic ossification. Nature Communications 2025, 16: 749. PMID: 39820504, PMCID: PMC11739514, DOI: 10.1038/s41467-025-56112-5.Peer-Reviewed Original ResearchConceptsStem/progenitor cellsHeterotopic bone formationTendon stem/progenitor cellsHeterotopic ossificationTendon healingCell populationsStem-progenitor cell populationBone formationProgenitor cell populationsStem cell populationMultipotent differentiation potentialSubstantial painCD26Self-renewalDifferentiation potentialTenascin-CTendon repairHealingOssificationCellsTendonPainSuppressed chondrogenesis
2024
The dynamics of hematopoiesis over the human lifespan
Li H, Côté P, Kuoch M, Ezike J, Frenis K, Afanassiev A, Greenstreet L, Tanaka-Yano M, Tarantino G, Zhang S, Whangbo J, Butty V, Moiso E, Falchetti M, Lu K, Connelly G, Morris V, Wang D, Chen A, Bianchi G, Daley G, Garg S, Liu D, Chou S, Regev A, Lummertz da Rocha E, Schiebinger G, Rowe R. The dynamics of hematopoiesis over the human lifespan. Nature Methods 2024, 22: 422-434. PMID: 39639169, PMCID: PMC11908799, DOI: 10.1038/s41592-024-02495-0.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsHematopoietic stemProgenitor cellsClassification of acute myeloid leukemiaDifferentiation of hematopoietic stem cellsAssociated with poor prognosisAcute myeloid leukemiaHuman hematopoietic stemWave of hematopoiesisGene expression networksMyeloid leukemiaPoor prognosisLineage outputMultilineage capacityDynamics of hematopoiesisCell ontogenyStem cellsLineage primingFate decisionsModel organismsTranscriptomic statesExpression networksHuman lifespanTranscriptional programsHematopoiesisEzrin drives adaptation of monocytes to the inflamed lung microenvironment
Gudneppanavar R, Di Pietro C, H Öz H, Zhang P, Cheng E, Huang P, Tebaldi T, Biancon G, Halene S, Hoppe A, Kim C, Gonzalez A, Krause D, Egan M, Gupta N, Murray T, Bruscia E. Ezrin drives adaptation of monocytes to the inflamed lung microenvironment. Cell Death & Disease 2024, 15: 864. PMID: 39613751, PMCID: PMC11607083, DOI: 10.1038/s41419-024-07255-8.Peer-Reviewed Original ResearchConceptsActivation of focal adhesion kinaseExtracellular matrixActin-binding proteinsFocal adhesion kinaseLung extracellular matrixKnock-out mouse modelProtein kinase signalingCortical cytoskeletonLoss of ezrinKinase signalingPlasma membraneCell migrationSignaling pathwayEzrinResponse to lipopolysaccharideTissue-resident macrophagesMouse modelLipopolysaccharideCytoskeletonEzrin expressionLung microenvironmentKinaseMonocyte recruitmentProteinAktDon’t be so naïve
Horsley V, Nassereddine A. Don’t be so naïve. ELife 2024, 13: e103292. PMID: 39453398, PMCID: PMC11509665, DOI: 10.7554/elife.103292.Peer-Reviewed Original ResearchTranscription factor TCF1 binds to RORγt and orchestrates a regulatory network that determines homeostatic Th17 cell state
Mangani D, Subramanian A, Huang L, Cheng H, Krovi S, Wu Y, Yang D, Moreira T, Escobar G, Schnell A, Dixon K, Krishnan R, Singh V, Sobel R, Weiner H, Kuchroo V, Anderson A. Transcription factor TCF1 binds to RORγt and orchestrates a regulatory network that determines homeostatic Th17 cell state. Immunity 2024, 57: 2565-2582.e6. PMID: 39447575, PMCID: PMC11614491, DOI: 10.1016/j.immuni.2024.09.017.Peer-Reviewed Original ResearchConceptsCell statesRegulatory networksSpectrum of cell statesTh17 cellsTranscription factor TPro-inflammatory Th17 cellsHomeostatic tissue functionReceptor signalingMature T cellsAutoimmune tissue damageInterleukin (IL)-23Controlling tissue inflammationPro-inflammatory functionsPro-inflammatory cellsConditional deletionDevelopment of therapiesRestore homeostasisPro-inflammatory potentialTCF1T-helperT cellsRORgtTissue inflammationCellsInflammatory diseasesNeuropeptide signalling orchestrates T cell differentiation
Hou Y, Sun L, LaFleur M, Huang L, Lambden C, Thakore P, Geiger-Schuller K, Kimura K, Yan L, Zang Y, Tang R, Shi J, Barilla R, Deng L, Subramanian A, Wallrapp A, Choi H, Kye Y, Ashenberg O, Schiebinger G, Doench J, Chiu I, Regev A, Sharpe A, Kuchroo V. Neuropeptide signalling orchestrates T cell differentiation. Nature 2024, 635: 444-452. PMID: 39415015, DOI: 10.1038/s41586-024-08049-w.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 3AnimalsCalcitonin Gene-Related PeptideCalcitonin Receptor-Like ProteinCell DifferentiationCyclic AMP Response Element-Binding ProteinFemaleMaleMiceMice, Inbred C57BLReceptor Activity-Modifying Protein 3Signal TransductionSTAT1 Transcription FactorTh1 CellsTh2 CellsConceptsT helper type 1Acute viral infectionActivating transcription factor 3Th1 cell differentiationCAMP response element-binding proteinViral infectionCell differentiationNeuropeptide CGRPFate determinationT cellsCD8+ T cell responsesDifferentiation of Th2 cellsIn vitro polarizationT cell fate determinationT cell responsesTh1 cell responsesCell fate determinationIn vivo CRISPR screeningDownstream cAMP response element-binding proteinT cell differentiationT helper cell differentiationIn vivo differentiationResponse element-binding proteinElement-binding proteinNeuroimmune circuitsNeuroendocrine Differentiation in Prostate Cancer Requires ASCL1.
Rodarte K, Nir Heyman S, Guo L, Flores L, Savage T, Villarreal J, Deng S, Xu L, Shah R, Oliver T, Johnson J. Neuroendocrine Differentiation in Prostate Cancer Requires ASCL1. Cancer Research 2024, 84: 3522-3537. PMID: 39264686, PMCID: PMC11534540, DOI: 10.1158/0008-5472.can-24-1388.Peer-Reviewed Original ResearchConceptsLoss of RB1Prostate cancerAndrogen receptorEmergence of treatment resistanceGenetically engineered mouse modelsLoss of ASCL1Luminal-like tumorsNeuroendocrine prostate cancerDecreased tumor incidencePoor survival outcomesTranscription factor Ascl1In vivo modelsNE differentiationProstatic adenocarcinomaNeuroendocrine differentiationAllograft tumorsProstate organoidsSurvival outcomesLineage plasticityTreatment resistanceNE featuresTumor incidenceNE lineageProgressive cancerAggressive formClass Effect Unveiled: PPARγ Agonists and MEK Inhibitors in Cancer Cell Differentiation
Ben-Yishay R, Globus O, Balint-Lahat N, Arbili-Yarhi S, Bar-Hai N, Bar V, Aharon S, Kosenko A, Zundelevich A, Berger R, Ishay-Ronen D. Class Effect Unveiled: PPARγ Agonists and MEK Inhibitors in Cancer Cell Differentiation. Cells 2024, 13: 1506. PMID: 39273076, PMCID: PMC11394433, DOI: 10.3390/cells13171506.Peer-Reviewed Original ResearchConceptsMEK inhibitorsBreast cancer cellsEpithelial-to-mesenchymal transitionCancer cellsPPARg agonistsDrug resistanceTherapeutic approachesTriple-negative breast cancerMurine breast cancer cellsAggressive breast cancer subtypeDevelopment of drug resistanceCancer cell plasticityBreast cancer subtypesCombination of pioglitazoneOvercome drug resistanceDedifferentiated cancer cellsBreast cancer progressionCancer cell differentiationCytoskeleton rearrangementLipid droplet accumulationCell trans-differentiationBreast cancerCancer subtypesCell plasticityTherapeutic strategiesMitochondrial network reorganization and transient expansion during oligodendrocyte generation
Bame X, Hill R. Mitochondrial network reorganization and transient expansion during oligodendrocyte generation. Nature Communications 2024, 15: 6979. PMID: 39143079, PMCID: PMC11324877, DOI: 10.1038/s41467-024-51016-2.Peer-Reviewed Original ResearchConceptsDecreased mitochondrial sizeLoss of mitochondriaMitochondrial motilityMitochondrial dynamicsCellular checkpointsMitochondrial distributionMitochondrial sizeMitochondrial contentOligodendrocyte precursor cellsSubcellular partitioningDistal processesMotilityOligodendrocyte generationOligodendrocyte processesLocal microenvironmentPrecursor cellsExtensive expansionMitochondriaOligodendrocyte lineageTransient expansionLineagesOligodendrocytesAging brainMyelinating oligodendrocytesMorphometricsMultiscale modeling uncovers 7q11.23 copy number variation–dependent changes in ribosomal biogenesis and neuronal maturation and excitability
Mihailovich M, Germain P, Shyti R, Pozzi D, Noberini R, Liu Y, Aprile D, Tenderini E, Troglio F, Trattaro S, Fabris S, Ciptasari U, Rigoli M, Caporale N, D’Agostino G, Mirabella F, Vitriolo A, Capocefalo D, Skaros A, Franchini A, Ricciardi S, Biunno I, Neri A, Kasri N, Bonaldi T, Aebersold R, Matteoli M, Testa G. Multiscale modeling uncovers 7q11.23 copy number variation–dependent changes in ribosomal biogenesis and neuronal maturation and excitability. Journal Of Clinical Investigation 2024, 134: e168982. PMID: 39007270, PMCID: PMC11245157, DOI: 10.1172/jci168982.Peer-Reviewed Original ResearchConceptsCopy number variationsWilliams-Beuren syndromeRibosome biogenesisP-RPS6Neurodevelopmental disordersRibosomal genesP-4EBPNumber variationsTranslation factorsMicroduplication syndromeMolecular mechanismsGenesNeuronal differentiationPatient-derivedIntrinsic excitabilityMTOR pathwayBiogenesisNeuronal maturationPhosphorylated rpS6Neuronal transmissionWilliams-BeurenPathophysiological relevanceNeurocognitive featuresIntellectual disabilityDisease modelsHemodynamics regulate spatiotemporal artery muscularization in the developing circle of Willis
Cheng S, Xia I, Wanner R, Abello J, Stratman A, Nicoli S. Hemodynamics regulate spatiotemporal artery muscularization in the developing circle of Willis. ELife 2024, 13: rp94094. PMID: 38985140, PMCID: PMC11236418, DOI: 10.7554/elife.94094.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCircle of WillisEndothelial CellsHemodynamicsHumansMuscle, Smooth, VascularMyocytes, Smooth MuscleZebrafishConceptsVascular smooth muscle cellsWall shear stressVascular smooth muscle cell differentiationVSMC differentiationEndothelial cellsAnalysis of blood flowBlood flowShear stressBrain arteriesPulsatile flowCerebrovascular diseaseDedifferentiated vascular smooth muscle cellsRegulate cerebral blood flowSmooth muscle cellsRed blood cell velocityDedifferentiation of vascular smooth muscle cellsCerebral blood flowBlood cell velocityArterial muscularizationVenous plexusCell progenitorsMuscle cellsBlood flow activationArteryFlowA humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses
Chupp D, Rivera C, Zhou Y, Xu Y, Ramsey P, Xu Z, Zan H, Casali P. A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses. Nature Immunology 2024, 25: 1489-1506. PMID: 38918608, PMCID: PMC11291283, DOI: 10.1038/s41590-024-01880-3.Peer-Reviewed Original ResearchConceptsB cellsImmune cell differentiationAntibody responseHumanized micePfizer-BioNTech coronavirus disease 2019T cell antigen receptor repertoireFollicular helper T cellsGerminal center B cellsHuman cord blood CD34Human thymic epithelial cellsT cell-independent antibody responsesImmune systemMarginal zone B cellsMaturation of antibody responsesMemory B cell differentiationCD34+ cellsCord blood CD34Helper T cellsT cell-dependentThymic epithelial cellsNeutralizing antibody responsesB cell differentiationHuman B cellsAntigen receptor repertoireCell differentiationQuantifying cell-state densities in single-cell phenotypic landscapes using Mellon
Otto D, Jordan C, Dury B, Dien C, Setty M. Quantifying cell-state densities in single-cell phenotypic landscapes using Mellon. Nature Methods 2024, 21: 1185-1195. PMID: 38890426, DOI: 10.1038/s41592-024-02302-w.Peer-Reviewed Original ResearchThe aMPPle differentiation potential of TH2 cells in human allergy.
Siddapureddy S, Eisenbarth S. The aMPPle differentiation potential of TH2 cells in human allergy. Science Immunology 2024, 9: eadq7287. PMID: 38848341, DOI: 10.1126/sciimmunol.adq7287.Peer-Reviewed Original ResearchRedefining intestinal stemness: The emergence of a new ISC population
Li M, Sumigray K. Redefining intestinal stemness: The emergence of a new ISC population. Cell 2024, 187: 2900-2902. PMID: 38848673, DOI: 10.1016/j.cell.2024.04.021.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationHomeostasisHumansIntestinal MucosaIntestinesMiceReceptors, G-Protein-CoupledStem CellsBone marrow mesenchymal stem cell-derived exosomes shuttle microRNAs to endometrial stromal fibroblasts that promote tissue proliferation /regeneration/ and inhibit differentiation
Bonavina G, Mamillapalli R, Krikun G, Zhou Y, Gawde N, Taylor H. Bone marrow mesenchymal stem cell-derived exosomes shuttle microRNAs to endometrial stromal fibroblasts that promote tissue proliferation /regeneration/ and inhibit differentiation. Stem Cell Research & Therapy 2024, 15: 129. PMID: 38693588, PMCID: PMC11064399, DOI: 10.1186/s13287-024-03716-1.Peer-Reviewed Original ResearchMeSH KeywordsBone Marrow CellsCell DifferentiationCell ProliferationEndometriumExosomesFemaleFibroblastsHumansMesenchymal Stem CellsMicroRNAsRegenerationConceptsMiR-100-5pMiR-100MiR-21Transmission electron microscopyMiR-143MiR-143-3pMiR-21-5pEndometrial stromal fibroblastsStromal fibroblastsMicroRNAsExtracellular vesiclesElectron microscopyCell-free regenerative therapyNanoparticle tracking analysisMiRNAsBone marrow mesenchymal stem cell-derived exosomesBone marrow-derived stem cellsMesenchymal stem cell-derived exosomesStem cell-derived exosomesDelivery of microRNAsMarrow-derived stem cellsAssociated with several signaling pathwaysMediators of tissue repairMethodsExtracellular vesiclesUnpaired t-test
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