2025
Subcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease
Cai Y, Kanyo J, Wilson R, Bathla S, Cardozo P, Tong L, Qin S, Fuentes L, Pinheiro-de-Sousa I, Huynh T, Sun L, Mansuri M, Tian Z, Gan H, Braker A, Trinh H, Huttner A, Lam T, Petsalaki E, Brennand K, Nairn A, Grutzendler J. Subcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease. Nature Aging 2025, 5: 504-527. PMID: 40065072, PMCID: PMC11922768, DOI: 10.1038/s43587-025-00823-3.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseProximity labeling approachIPSC-derived neuronsSubcellular proteomicsCytoskeleton dynamicsPhosphorylated mTOR levelsDystrophic neuritesLipid transportBiological processesProtein turnoverAD modelHuman induced pluripotent stem cellsAmyloid depositsIPSC modelsProteomicsInduced pluripotent stem cellsPluripotent stem cellsMTOR inhibitionTherapeutic targetAxonal pathologyLabeling approachMTOR levelsMouse brainSpheroid formationAlzheimerModeling 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 consequences
2024
Vascular endothelial cells derived from transgene-free pig induced pluripotent stem cells for vascular tissue engineering
Batty L, Park J, Qin L, Riaz M, Lin Y, Xu Z, Gao X, Li X, Lopez C, Zhang W, Hoareau M, Fallon M, Huang Y, Luo H, Luo J, Ménoret S, Li P, Jiang Z, Smith P, Sachs D, Tellides G, Anegon I, Pober J, Liu P, Qyang Y. Vascular endothelial cells derived from transgene-free pig induced pluripotent stem cells for vascular tissue engineering. Acta Biomaterialia 2024, 193: 171-184. PMID: 39681154, DOI: 10.1016/j.actbio.2024.12.033.Peer-Reviewed Original ResearchThis study created transgene-free pig induced pluripotent stem cells for engineered blood vessels that prevent clots, opening new possibilities for modeling improved cardiovascular treatments.209 Transcriptomic Analysis of the Post-mortem Brain in Intracranial Atherosclerosis Implicates Interferon Signaling
Seah C, Devarajan A, Jurczyszak D, Chakka A, Huckins L, Brennand K, Girgenti M. 209 Transcriptomic Analysis of the Post-mortem Brain in Intracranial Atherosclerosis Implicates Interferon Signaling. Neurosurgery 2024, 70: 55-56. DOI: 10.1227/neu.0000000000002809_209.Peer-Reviewed Original ResearchIntracranial atherosclerotic stenosisIntracranial arteriesInterferon-inducible genesInterferon signalingPeripheral atherosclerosisCerebral atherosclerosisExpression of interferon-inducible genesGlial cellsSymptomatic intracranial atherosclerotic stenosisInduced pluripotent stem cellsPost-mortem brainsWorsened functional outcomesHuman induced pluripotent stem cellsUpregulation of interferon inducible genesCause of ischemic strokePluripotent stem cellsRisk of atherosclerosisLipid-rich plaquesRisk factor managementClinical outcomesPoor prognosisExcitatory neuronsIncreased morbidityHistopathological profileFunctional outcomes
2023
Modelling post-implantation human development to yolk sac blood emergence
Hislop J, Song Q, Keshavarz F. K, Alavi A, Schoenberger R, LeGraw R, Velazquez J, Mokhtari T, Taheri M, Rytel M, Chuva de Sousa Lopes S, Watkins S, Stolz D, Kiani S, Sozen B, Bar-Joseph Z, Ebrahimkhani M. Modelling post-implantation human development to yolk sac blood emergence. Nature 2023, 626: 367-376. PMID: 38092041, PMCID: PMC10849971, DOI: 10.1038/s41586-023-06914-8.Peer-Reviewed Original ResearchConceptsHuman embryosInduced pluripotent stem cellsLymphoid-like cellsStem cell modelPluripotent stem cellsPost-implantation stagesAmniotic cavityEarly post-implantation stagesHuman-based modelsStem cellsExtra-embryonic endodermHuman embryogenesisBlood formationDrug testingEarly haematopoiesisDisease modelsDisc morphologyHaematopoiesisEmbryonic tissuesCellular programmeCell modelPosterior domainDNA methylation of the promoter region at the CREB1 binding site is a mechanism for the epigenetic regulation of brain-specific PKMζ
Pramio D, Vieceli F, Varella-Branco E, Goes C, Kobayashi G, da Silva Pelegrina D, de Moraes B, El Allam A, De Kumar B, Jara G, Farfel J, Bennett D, Kundu S, Viapiano M, Reis E, de Oliveira P, Dos Santos E Passos-Bueno M, Rothlin C, Ghosh S, Schechtman D. DNA methylation of the promoter region at the CREB1 binding site is a mechanism for the epigenetic regulation of brain-specific PKMζ. Biochimica Et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 2023, 1866: 194909. PMID: 36682583, PMCID: PMC10037092, DOI: 10.1016/j.bbagrm.2023.194909.Peer-Reviewed Original ResearchConceptsInduced pluripotent stem cellsInternal promoterNeuronal differentiationEpigenetic mechanismsDNA methylationUpstream promoterProtein kinase C ζHuman neuronal differentiationSite-specific hypermethylationAberrant DNA hypermethylationPluripotent stem cellsEpigenetic regulationSame epigenetic mechanismsLong-term memory formationDNA hypermethylationDemethylated regionsEpigenetic factorsPromoter regionTissue specificityMolecular mechanismsPRKCZ geneDifferentiated neuronsPromoterProtein kinase M zetaLong-term potentiation
2022
Transcriptional Dysregulation Underlies Both Monogenic Arrhythmia Syndrome and Common Modifiers of Cardiac Repolarization
Bersell K, Yang T, Mosley J, Glazer A, Hale A, Kryshtal D, Kim K, Steimle J, Brown J, Salem J, Campbell C, Hong C, Wells Q, Johnson A, Short L, Blair M, Behr E, Petropoulou E, Jamshidi Y, Benson M, Keyes M, Ngo D, Vasan R, Yang Q, Gerszten R, Shaffer C, Parikh S, Sheng Q, Kannankeril P, Moskowitz I, York J, Wang T, Knollmann B, Roden D. Transcriptional Dysregulation Underlies Both Monogenic Arrhythmia Syndrome and Common Modifiers of Cardiac Repolarization. Circulation 2022, 147: 824-840. PMID: 36524479, PMCID: PMC9992308, DOI: 10.1161/circulationaha.122.062193.Peer-Reviewed Original ResearchConceptsPlatelet-derived growth factorInduced pluripotent stem cellsBrugada syndromeArrhythmia syndromesSerum platelet-derived growth factorSodium currentGeneral transcriptional mechanismFramingham Heart Study cohortPI3KPDGF receptor expressionLate sodium currentCardiac sodium currentCardiac transcription factorsSmall molecule perturbationsCurrent-clamp experimentsCardiac sodium channel geneSodium channel geneFramingham Heart StudyMurine model systemPluripotent stem cellsMonogenic arrhythmia syndromesReceptor blockadeElectrophysiologic abnormalitiesQTc intervalStudy cohortReduced LYNX1 expression in transcriptome of human iPSC-derived neural progenitors modeling fragile X syndrome
Talvio K, Minkeviciene R, Townsley K, Achuta V, Huckins L, Corcoran P, Brennand K, Castrén M. Reduced LYNX1 expression in transcriptome of human iPSC-derived neural progenitors modeling fragile X syndrome. Frontiers In Cell And Developmental Biology 2022, 10: 1034679. PMID: 36506088, PMCID: PMC9731341, DOI: 10.3389/fcell.2022.1034679.Peer-Reviewed Original ResearchInduced pluripotent stem cellsFragile X syndromeHuman induced pluripotent stem cellsNeural progenitorsX syndromeEarly gene expression changesGene expression changesPatient-derived induced pluripotent stem cellsTriplet repeat instabilityFunctional enrichment analysisHuman neural progenitorsPluripotent stem cellsRNA splicingPhenotypic variationIntellectual disability syndromeEnrichment analysisExpression changesRepeat instabilityMolecular mechanismsProtein resultsGrowth factor pathwaysInsulin-like growth factor (IGF) pathwayAltered expressionStem cellsTranscriptomeReadily Available Tissue-Engineered Vascular Grafts Derived From Human Induced Pluripotent Stem Cells
Luo J, Qin L, Park J, Kural MH, Huang Y, Shi X, Riaz M, Wang J, Ellis MW, Anderson CW, Yuan Y, Ren Y, Yoder MC, Tellides G, Niklason LE, Qyang Y. Readily Available Tissue-Engineered Vascular Grafts Derived From Human Induced Pluripotent Stem Cells. Circulation Research 2022, 130: 925-927. PMID: 35189711, PMCID: PMC9113663, DOI: 10.1161/circresaha.121.320315.Peer-Reviewed Original ResearchConceptsVascular graftsAvailable tissueHuman induced pluripotent stem cellsInduced pluripotent stem cells
2021
Epigallocatechin gallate facilitates extracellular elastin fiber formation in induced pluripotent stem cell derived vascular smooth muscle cells for tissue engineering
Ellis MW, Riaz M, Huang Y, Anderson CW, Luo J, Park J, Lopez CA, Batty LD, Gibson KH, Qyang Y. Epigallocatechin gallate facilitates extracellular elastin fiber formation in induced pluripotent stem cell derived vascular smooth muscle cells for tissue engineering. Journal Of Molecular And Cellular Cardiology 2021, 163: 167-174. PMID: 34979103, PMCID: PMC8920537, DOI: 10.1016/j.yjmcc.2021.12.014.Peer-Reviewed Original ResearchConceptsPluripotent stem cellsTissue engineeringStem cell derivativesPluripotent stem cell derivativesInduced pluripotent stem cellsStem cellsGraft productionMechanical strengthExtracellular formationExpression systemCell derivativesVascular smooth muscle cellsElastin fiber formationEngineered graftSmooth muscle cellsFiber formationNotable obstacleLack of elastinMuscle cellsEngineeringClinical applicationVascular graftsCell proliferative capacityElastin productionProliferative capacityMethods for Differentiating hiPSCs into Vascular Smooth Muscle Cells
Li ML, Luo J, Ellis MW, Riaz M, Ajaj Y, Qyang Y. Methods for Differentiating hiPSCs into Vascular Smooth Muscle Cells. Methods In Molecular Biology 2021, 2375: 21-34. PMID: 34591296, DOI: 10.1007/978-1-0716-1708-3_3.Peer-Reviewed Original ResearchConceptsHuman induced pluripotent stem cellsVascular smooth muscle cellsPluripotent stem cellsLateral plate mesodermEarly embryonic developmentStem cellsSmooth muscle cellsHuman pluripotent stem cellsInduced pluripotent stem cellsExtracellular matrix proteinsMuscle cellsMesoderm lineagePlate mesodermEmbryonic developmentVascular cell sourceEmbryoid bodiesEB formationMatrix proteinsCellular interactionsDisease modelingPhysiological characteristicsVascular tissueTissue-engineered vascular graftsCell-based therapiesCell replacementUnlocking the Potential of Induced Pluripotent Stem Cells for Wound Healing: The Next Frontier of Regenerative Medicine
Dash BC, Korutla L, Vallabhajosyula P, Hsia HC. Unlocking the Potential of Induced Pluripotent Stem Cells for Wound Healing: The Next Frontier of Regenerative Medicine. Advances In Wound Care 2021, 11: 622-638. PMID: 34155919, DOI: 10.1089/wound.2021.0049.Peer-Reviewed Original ResearchConceptsInduced pluripotent stem cell (iPSC) technologyTissue-engineered skin constructsSkin constructsSkin tissue engineeringStem cell technologyPluripotent stem cell (iPSC) technologyInduced pluripotent stem cellsPluripotent stem cellsCell-based therapiesRegenerative medicineTissue engineeringCell technologyCurrent advancementsTissue regenerationDisease modelingHiPSC linesEfficient manufacturing processesIPSC linesCurrent progressFunctional cellsLarge animal studiesNext generationJazf1 acts as a regulator of insulin‐producing β‐cell differentiation in induced pluripotent stem cells and glucose homeostasis in mice
Park S, Kwon W, Park S, Jeong J, Kim D, Jang S, Kim S, Sung Y, Kim M, Choi S, Ryoo Z. Jazf1 acts as a regulator of insulin‐producing β‐cell differentiation in induced pluripotent stem cells and glucose homeostasis in mice. The FEBS Journal 2021, 288: 4412-4427. PMID: 33555104, DOI: 10.1111/febs.15751.Peer-Reviewed Original ResearchAltered transcriptome and disease-related phenotype emerge only after fibroblasts harvested from patients with age-related macular degeneration are differentiated into retinal pigment epithelium
Cai H, Gong J, Team N, Noggle S, Paull D, Rizzolo LJ, Del Priore LV, Fields MA. Altered transcriptome and disease-related phenotype emerge only after fibroblasts harvested from patients with age-related macular degeneration are differentiated into retinal pigment epithelium. Experimental Eye Research 2021, 207: 108576. PMID: 33895162, DOI: 10.1016/j.exer.2021.108576.Peer-Reviewed Original ResearchConceptsAge-related macular degenerationRetinal pigment epitheliumMacular degenerationPigment epitheliumInduced pluripotent stem cellsEtiology of AMDMitochondrial dysfunctionAge-matched controlsNovel therapeutic targetTranscriptome of fibroblastsAMD patientsNormal donorsFibroblasts of patientsTherapeutic targetPatientsMore studiesAltered transcriptomeDisease phenotypeSignificant differencesCell linesMitochondrial functionDysfunctionOriginal fibroblastsDistinct transcriptomesDegenerationMachine learning-assisted high-content analysis of pluripotent stem cell-derived embryos in vitro
Guo J, Wang P, Sozen B, Qiu H, Zhu Y, Zhang X, Ming J, Zernicka-Goetz M, Na J. Machine learning-assisted high-content analysis of pluripotent stem cell-derived embryos in vitro. Stem Cell Reports 2021, 16: 1331-1346. PMID: 33891867, PMCID: PMC8185434, DOI: 10.1016/j.stemcr.2021.03.018.Peer-Reviewed Original ResearchCircadian rhythms in bipolar disorder patient-derived neurons predict lithium response: preliminary studies
Mishra H, Ying N, Luis A, Wei H, Nguyen M, Nakhla T, Vandenburgh S, Alda M, Berrettini W, Brennand K, Calabrese J, Coryell W, Frye M, Gage F, Gershon E, McInnis M, Nievergelt C, Nurnberger J, Shilling P, Oedegaard K, Zandi P, Kelsoe J, Welsh D, McCarthy M. Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response: preliminary studies. Molecular Psychiatry 2021, 26: 3383-3394. PMID: 33674753, PMCID: PMC8418615, DOI: 10.1038/s41380-021-01048-7.Peer-Reviewed Original ResearchConceptsNeuronal precursor cellsBipolar disorderCircadian rhythm abnormalitiesRhythm abnormalitiesBD groupCircadian rhythmPatient-derived neuronsMania/hypomaniaExpression of Per2Induced pluripotent stem cellsPER2 protein levelsGlutamatergic neuronsRecurrent episodesBD patientsControl neuronsLithium respondersEffective drugsNeuropsychiatric illnessLithium responsivenessPatient neuronsNeuronsLithium responseProtein levelsRhythm deficitsPrecursor cells
2020
Induced pluripotent stem cell reprogramming‐associated methylation at the GABRA2 promoter and chr4p12 GABAA subunit gene expression in the context of alcohol use disorder
Goetjen A, Watson M, Lieberman R, Clinton K, Kranzler H, Covault J. Induced pluripotent stem cell reprogramming‐associated methylation at the GABRA2 promoter and chr4p12 GABAA subunit gene expression in the context of alcohol use disorder. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2020, 183: 464-474. PMID: 33029895, PMCID: PMC8022112, DOI: 10.1002/ajmg.b.32824.Peer-Reviewed Original ResearchConceptsGene expressionSubunit gene expressionSubunit geneNeural culturesInduced pluripotent stem cellsReceptor subunit genesPluripotent stem cellsStochastic methylationGene clusterDNA methylationCpG methylationMethylation levelsReceptor subunit gene expressionMethylationSignificant genetic contributionGenesStem cellsGenetic contributionMolecular effectsIPSC linesGABRB1 geneExpressionGABRA2GenotypesAdditive effectMitomycin-C treatment during differentiation of induced pluripotent stem cell-derived dopamine neurons reduces proliferation without compromising survival or function in vivo
Hiller B, Marmion D, Gross R, Thompson C, Chavez C, Brundin P, Wakeman D, McMahon C, Kordower J. Mitomycin-C treatment during differentiation of induced pluripotent stem cell-derived dopamine neurons reduces proliferation without compromising survival or function in vivo. Stem Cells Translational Medicine 2020, 10: 278-290. PMID: 32997443, PMCID: PMC7848297, DOI: 10.1002/sctm.20-0014.Peer-Reviewed Original ResearchConceptsDopamine neuronsInduced pluripotent stem cellsParkinson's diseaseStem cell-derived dopamine neuronsPD cell therapyMidbrain dopamine neuronsLong-term survivalTransplant of cellsStem cellsHuman induced pluripotent stem cellsPluripotent stem cellsNeuron preparationsMitomycin C treatmentAthymic ratsDrug selectionUndesirable proliferationCell therapyRobust survivalLower proliferationVivo functionNeuronsTransplantationSurvivalProliferative cellsDiseaseGeneration of Pluripotent Stem Cells Using Somatic Cell Nuclear Transfer and Induced Pluripotent Somatic Cells from African Green Monkeys
Chung YG, Seay M, Elsworth J, Redmond D. Generation of Pluripotent Stem Cells Using Somatic Cell Nuclear Transfer and Induced Pluripotent Somatic Cells from African Green Monkeys. Stem Cells And Development 2020, 29: 1294-1307. PMID: 32715987, DOI: 10.1089/scd.2020.0059.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCell LineChlorocebus aethiopsChromosome BandingCloning, OrganismCulture MediaCytogenetic AnalysisDNADopaminergic NeuronsEmbryonic DevelopmentEmbryonic Stem CellsFemaleGenotypeHumansInduced Pluripotent Stem CellsMitochondriaNuclear Transfer TechniquesOvaryTyrosine 3-MonooxygenaseConceptsAfrican green monkeysInduced pluripotent stem cellsCell linesGreen monkeysStem cellsEffective cell replacement therapyPromising potential therapyPluripotent stem cellsDopamine depletionReplacement therapyDopamine neuronsCell replacement therapyBrain pathologyDonor monkeyParkinson's diseasePotential therapyMonkey studiesFemale monkeysClinical predictive powerImmune rejectionImmune systemAccidental exposurePossible treatmentIPSC linesRodent experimentsIntegrating CRISPR Engineering and hiPSC-Derived 2D Disease Modeling Systems
Rehbach K, Fernando MB, Brennand KJ. Integrating CRISPR Engineering and hiPSC-Derived 2D Disease Modeling Systems. Journal Of Neuroscience 2020, 40: 1176-1185. PMID: 32024766, PMCID: PMC7002154, DOI: 10.1523/jneurosci.0518-19.2019.Peer-Reviewed Original ResearchConceptsHuman induced pluripotent stem cellsMajor brain cell typesDual Perspectives CompanionBrain cell typesNeuronal maturityPsychiatric disordersHuman neuronsDisease riskStudy designBrain organoidsIntradonor variabilityDisease modelsHuman neurodevelopmentInduced pluripotent stem cellsNeural differentiationDiseaseStem cellsCell typesPluripotent stem cellsHuman diseasesEfficient neural differentiationInduction strategyPatient-specific cellsDisease modelingCells
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