2021
Vulnerability of cholecystokinin-expressing GABAergic interneurons in the unilateral intrahippocampal kainate mouse model of temporal lobe epilepsy
Kang YJ, Clement EM, Park IH, Greenfield LJ, Smith BN, Lee SH. Vulnerability of cholecystokinin-expressing GABAergic interneurons in the unilateral intrahippocampal kainate mouse model of temporal lobe epilepsy. Experimental Neurology 2021, 342: 113724. PMID: 33915166, PMCID: PMC8192495, DOI: 10.1016/j.expneurol.2021.113724.Peer-Reviewed Original ResearchConceptsTemporal lobe epilepsyIntrahippocampal kainate mouse modelVentral CA1 regionEpileptic miceCA1 pyramidal cellsSclerotic hippocampusPyramidal cellsSham controlsSpontaneous seizuresLobe epilepsyCA1 regionMouse modelFrequency of IPSCsNetwork oscillationsRecurrent spontaneous seizuresNumber of boutonsHippocampal theta oscillationsIpsilateral hippocampusElectrical recordingsVentral hippocampusCA1 layerGABAergic interneuronsStratum pyramidaleDorsal hippocampusBehavioral comorbidities
2020
Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations
Wang K, Zhang H, He Y, Jiang Q, Tanaka Y, Park IH, Pober JS, Min W, Zhou HJ. Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations. Arteriosclerosis Thrombosis And Vascular Biology 2020, 40: 2171-2186. PMID: 32640906, DOI: 10.1161/atvbaha.120.314586.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsBrainCell CommunicationCell MovementCells, CulturedCoculture TechniquesEndothelial CellsFemaleFocal AdhesionsGene DeletionGenetic Predisposition to DiseaseHemangioma, Cavernous, Central Nervous SystemHumansMaleMembrane ProteinsMice, KnockoutMicrovesselsMyocytes, Smooth MusclePaxillinPericytesPhenotypeProtein StabilityProto-Oncogene ProteinsSignal TransductionConceptsCerebral cavernous malformationsBrain mural cellsCCM lesionsMural cellsCavernous malformationsSevere brain hemorrhageCCM pathogenesisSmooth muscle cellsWeeks of ageCell-specific deletionMural cell coverageBrain pericytesBrain hemorrhageNeonatal stageBrain vasculatureLesionsEntire brainMuscle cellsCerebral cavernous malformation 3Endothelial cellsMicePericytesSpecific deletionAdhesion formationPathogenesisDysregulation of BRD4 Function Underlies the Functional Abnormalities of MeCP2 Mutant Neurons
Xiang Y, Tanaka Y, Patterson B, Hwang SM, Hysolli E, Cakir B, Kim KY, Wang W, Kang YJ, Clement EM, Zhong M, Lee SH, Cho YS, Patra P, Sullivan GJ, Weissman SM, Park IH. Dysregulation of BRD4 Function Underlies the Functional Abnormalities of MeCP2 Mutant Neurons. Molecular Cell 2020, 79: 84-98.e9. PMID: 32526163, PMCID: PMC7375197, DOI: 10.1016/j.molcel.2020.05.016.Peer-Reviewed Original ResearchConceptsMECP2 mutant neuronsEnhancer-promoter interactionsRett syndromeRTT-like phenotypesChromatin bindingMeCP2 functionMethyl-CpGAbnormal transcriptionRTT etiologyMutant neuronsBET inhibitorsPotential therapeutic opportunitiesMECP2 mutationsProtein 2Human brain organoidsFunctional phenotypeJQ1BRD4Therapeutic opportunitiesBrain organoidsFunction underliesMutationsPhenotypeHuman brain culturesCritical driverSynthetic Analyses of Single-Cell Transcriptomes from Multiple Brain Organoids and Fetal Brain
Tanaka Y, Cakir B, Xiang Y, Sullivan GJ, Park IH. Synthetic Analyses of Single-Cell Transcriptomes from Multiple Brain Organoids and Fetal Brain. Cell Reports 2020, 30: 1682-1689.e3. PMID: 32049002, PMCID: PMC7043376, DOI: 10.1016/j.celrep.2020.01.038.Peer-Reviewed Original Research
2018
Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a
Kim KY, Tanaka Y, Su J, Cakir B, Xiang Y, Patterson B, Ding J, Jung YW, Kim JH, Hysolli E, Lee H, Dajani R, Kim J, Zhong M, Lee JH, Skalnik D, Lim JM, Sullivan GJ, Wang J, Park IH. Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a. Nature Communications 2018, 9: 2583. PMID: 29968706, PMCID: PMC6030064, DOI: 10.1038/s41467-018-04818-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCCAAT-Enhancer-Binding ProteinsCellular ReprogrammingCellular Reprogramming TechniquesChimeraDNA MethylationEpigenesis, GeneticFemaleFibroblastsGene Knockout TechniquesHEK293 CellsHistone CodeHistone-Lysine N-MethyltransferaseHistonesHumansMaleMesodermMiceMouse Embryonic Stem CellsNeural PlateNuclear ProteinsPrimary Cell CultureRecombinant ProteinsUbiquitin-Protein LigasesConceptsEmbryonic stem cellsUnique epigenetic statesBivalent histone modificationsRecruitment of DNMT1Bivalent histone marksCell typesDNA-binding proteinsSpecialized cell typesStem cellsPluripotent stem cellsTrithorax groupBivalent domainsMesoderm specificationCOMPASS complexHeterochromatin formationEpigenetic stateCell specificationHistone marksLineage specificationHistone modificationsEpigenetic regulationSpecific lineagesDNA methylationTranscriptional marksEpigenetic changes
2017
Enhanced Therapeutic and Long-Term Dynamic Vascularization Effects of Human Pluripotent Stem Cell–Derived Endothelial Cells Encapsulated in a Nanomatrix Gel
Lee SJ, Sohn YD, Andukuri A, Kim S, Byun J, Han JW, Park IH, Jun HW, Yoon YS. Enhanced Therapeutic and Long-Term Dynamic Vascularization Effects of Human Pluripotent Stem Cell–Derived Endothelial Cells Encapsulated in a Nanomatrix Gel. Circulation 2017, 136: 1939-1954. PMID: 28972000, PMCID: PMC5685906, DOI: 10.1161/circulationaha.116.026329.Peer-Reviewed Original ResearchConceptsCell survivalHPSC-ECsHuman pluripotent stem cell-derived endothelial cellsEndothelial lineage differentiationGlycogen synthase kinase-3β inhibitorHuman pluripotent stem cellsStem cell-derived endothelial cellsGrowth factorDifferentiation of hPSCsLonger cell survivalEndothelial cellsCell-derived endothelial cellsVessel formationPluripotent stem cell-derived endothelial cellsBetter perfusion recoveryPluripotent stem cellsNanomatrix gelLong-term cell survivalMesodermal lineagesLineage differentiationHuman umbilical vein endothelial cellsUmbilical vein endothelial cellsDifferentiation systemFibroblast growth factorBasic fibroblast growth factor
2016
Direct Reprogramming of Human Dermal Fibroblasts Into Endothelial Cells Using ER71/ETV2
Lee S, Park C, Han JW, Kim JY, Cho K, Kim EJ, Kim S, Lee SJ, Oh SY, Tanaka Y, Park IH, An HJ, Shin CM, Sharma S, Yoon YS. Direct Reprogramming of Human Dermal Fibroblasts Into Endothelial Cells Using ER71/ETV2. Circulation Research 2016, 120: 848-861. PMID: 28003219, PMCID: PMC5336520, DOI: 10.1161/circresaha.116.309833.Peer-Reviewed Original ResearchConceptsEndothelial cellsPostnatal cellsCell therapyDermal fibroblastsMature endothelial cellsNew vessel formationEndothelial featuresHuman endothelial cellsHindlimb ischemiaIschemic hindlimbPathophysiological investigationsEndothelial transcription factorImmature phenotypeDay 7Therapeutic potentialVascular incorporationProangiogenic effectsMature phenotypeEndothelial characteristicsIschemiaVessel formationHuman dermal fibroblastsTranscription factorsTherapyDisease investigationSingle cell transcriptomics reveals unanticipated features of early hematopoietic precursors
Yang J, Tanaka Y, Seay M, Li Z, Jin J, Garmire LX, Zhu X, Taylor A, Li W, Euskirchen G, Halene S, Kluger Y, Snyder MP, Park IH, Pan X, Weissman SM. Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors. Nucleic Acids Research 2016, 45: 1281-1296. PMID: 28003475, PMCID: PMC5388401, DOI: 10.1093/nar/gkw1214.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsPrecursor cellsInduction of anemiaInterferon response genesG2/M phaseEarly precursor cellsHomeostatic cellsStages of differentiationTranscription factorsSurface markersCell cycle progressionLong-term hematopoietic stem cellsSpecific augmentationAnemic miceMarked increaseEarly hematopoietic precursorsHematopoietic precursorsStem cellsCycle progressionM phaseSingle-cell transcriptomicsCellsCell differentiationHematopoietic stressLineage-specific transcription factorsNeural Stem Cells Restore Hair Growth through Activation of the Hair Follicle Niche
Hwang I, Choi KA, Park HS, Jeong H, Kim JO, Seol KC, Kwon HJ, Park IH, Hong S. Neural Stem Cells Restore Hair Growth through Activation of the Hair Follicle Niche. Cell Transplantation 2016, 25: 1439-1451. PMID: 27110030, DOI: 10.3727/096368916x691466.Peer-Reviewed Original ResearchConceptsInsulin-like growth factor-1Shaven dorsal skinNeural stem cellsVascular endothelial growth factorDermal papilla cellsHepatocyte growth factorKeratinocyte growth factorGrowth factorHair follicle nicheHair growthDorsal skinStem cellsAnagen phaseGrowth factor-1Endothelial growth factorGrowth factor pathwaysCombined growth factorsMolecular signaling pathwaysPharmacological therapyHair regrowthHair shaft lengthBone morphogenetic protein family membersNSC treatmentProtein family membersHair follicle stem cells
2013
Therapeutic Potential of Human Induced Pluripotent Stem Cells in Experimental Stroke
Chang DJ, Lee N, Park IH, Choi C, Jeon I, Kwon J, Oh SH, Shin DA, Tae J, Lee DR, Lee H, Hong K, Daley G, Song J, Moon H. Therapeutic Potential of Human Induced Pluripotent Stem Cells in Experimental Stroke. Cell Transplantation 2013, 22: 1427-1440. PMID: 23044029, DOI: 10.3727/096368912x657314.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBehavior, AnimalCell DifferentiationCell LineCell TrackingDisease Models, AnimalGliosisHumansInduced Pluripotent Stem CellsInfarction, Middle Cerebral ArteryInflammationMagnetic Resonance ImagingMaleMiceNeural Stem CellsNeurogenesisNeuronsRatsRats, Sprague-DawleyStem Cell TransplantationStrokeConceptsMiddle cerebral artery occlusionNeural precursor cellsNeural stem cellsStroke-induced inflammatory responseTherapeutic potentialMCAO stroke modelCerebral artery occlusionPeri-infarct areaTreatment of strokeLimited therapeutic optionsStem cellsAutologous cell therapyEndogenous neurogenesisExperimental strokePluripotent stem cellsArtery occlusionIschemic strokeBehavioral recoveryTherapeutic optionsNeurological functionInflammatory responseRobust therapeutic potentialStroke modelMRI resultsAnimal models
2012
Development of a novel two-dimensional directed differentiation system for generation of cardiomyocytes from human pluripotent stem cells
Moon SH, Ban K, Kim C, Kim SS, Byun J, Song MK, Park IH, Yu SP, Yoon YS. Development of a novel two-dimensional directed differentiation system for generation of cardiomyocytes from human pluripotent stem cells. International Journal Of Cardiology 2012, 168: 41-52. PMID: 23044428, PMCID: PMC3556195, DOI: 10.1016/j.ijcard.2012.09.077.Peer-Reviewed Original ResearchModeling Supravalvular Aortic Stenosis Syndrome With Human Induced Pluripotent Stem Cells
Ge X, Ren Y, Bartulos O, Lee MY, Yue Z, Kim KY, Li W, Amos PJ, Bozkulak EC, Iyer A, Zheng W, Zhao H, Martin KA, Kotton DN, Tellides G, Park IH, Yue L, Qyang Y. Modeling Supravalvular Aortic Stenosis Syndrome With Human Induced Pluripotent Stem Cells. Circulation 2012, 126: 1695-1704. PMID: 22914687, PMCID: PMC3586776, DOI: 10.1161/circulationaha.112.116996.Peer-Reviewed Original ResearchConceptsActin filament bundlesSmooth muscle αSmooth muscle cellsExtracellular signal-regulated kinase 1/2Muscle αFilament bundlesSignal-regulated kinase 1/2Four-nucleotide insertionDisease mechanismsContractile smooth muscle cellsStem cell linesPluripotent stem cellsPluripotent stem cell linePlatelet-derived growth factorRhoA signalingVascular smooth muscle cellsRecombinant proteinsKinase 1/2Elastin geneELN geneWilliams-Beuren syndromeBrdU analysisSupravalvular aortic stenosisStem cellsHigh proliferation rateNeuronal Properties, In Vivo Effects, and Pathology of a Huntington's Disease Patient‐Derived Induced Pluripotent Stem Cells
Jeon I, Lee N, Li J, Park I, Park KS, Moon J, Shim SH, Choi C, Chang D, Kwon J, Oh S, Shin DA, Kim HS, Tae J, Lee DR, Kim M, Kang K, Daley GQ, Brundin P, Song J. Neuronal Properties, In Vivo Effects, and Pathology of a Huntington's Disease Patient‐Derived Induced Pluripotent Stem Cells. Stem Cells 2012, 30: 2054-2062. PMID: 22628015, DOI: 10.1002/stem.1135.Peer-Reviewed Original ResearchConceptsHD-iPSCHD pathologyHuntington's diseaseDisease patientsNeuronal propertiesUnilateral excitotoxic striatal lesionExcitotoxic striatal lesionsSignificant behavioral recoveryStem cellsGABAergic striatal neuronsHuntington's disease patientsCAG repeatsNeuronal cell typesPluripotent stem cellsBehavioral recoveryGABAergic neuronsStriatal lesionsStriatal neuronsRat modelNeonatal brainNovel cell therapiesVivo effectsHD phenotypeCell therapyNovel therapeuticsMutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability
Bilican B, Serio A, Barmada SJ, Nishimura AL, Sullivan GJ, Carrasco M, Phatnani HP, Puddifoot CA, Story D, Fletcher J, Park IH, Friedman BA, Daley GQ, Wyllie DJ, Hardingham GE, Wilmut I, Finkbeiner S, Maniatis T, Shaw CE, Chandran S. Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 5803-5808. PMID: 22451909, PMCID: PMC3326463, DOI: 10.1073/pnas.1202922109.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisTDP-43 proteinopathyTDP-43Human neuronsTransactive response DNA binding proteinFrontotemporal lobar degenerationFamilial amyotrophic lateral sclerosisFunctional motor neuronsCell-specific vulnerabilityTDP-43 proteinDNA binding proteinPI3K pathwayCell-autonomous phenotypeMotor neuronsLateral sclerosisStem cell linesPluripotent stem cellsGeneration of iPSCsIdentification of mutationsPluripotent stem cell lineMutant neuronsNeuronsK pathwayElevated levelsDisease mechanisms
2010
Hematopoietic differentiation of induced pluripotent stem cells from patients with mucopolysaccharidosis type I (Hurler syndrome)
Tolar J, Park IH, Xia L, Lees CJ, Peacock B, Webber B, McElmurry RT, Eide CR, Orchard PJ, Kyba M, Osborn MJ, Lund TC, Wagner JE, Daley GQ, Blazar BR. Hematopoietic differentiation of induced pluripotent stem cells from patients with mucopolysaccharidosis type I (Hurler syndrome). Blood 2010, 117: 839-847. PMID: 21037085, PMCID: PMC3035077, DOI: 10.1182/blood-2010-05-287607.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow CellsCell DifferentiationCells, CulturedChild, PreschoolDNA MethylationHEK293 CellsHematopoietic SystemHomeodomain ProteinsHumansIduronidaseInduced Pluripotent Stem CellsInfantKeratinocytesKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMesodermMiceMucopolysaccharidosis INanog Homeobox ProteinOctamer Transcription Factor-3Promoter Regions, GeneticProto-Oncogene Proteins c-mycSOXB1 Transcription FactorsStromal CellsTransfectionConceptsHematopoietic cell transplantationMPS IHMucopolysaccharidosis type IL-iduronidaseNonhematopoietic cellsStem cellsLife-saving measureInduced pluripotent stem cellsAutologous stem cellsAutologous hematopoietic graftsType IPluripotent stem cellsAllogeneic transplantationSignificant morbidityImmunologic complicationsInsidious onsetCell transplantationHematopoietic graftsImmune reactionsAnatomical sitesCongenital deficiencyIdeal graftDonor cellsLysosomal storageKnown benefits
2009
Generation of functional human hepatic endoderm from human induced pluripotent stem cells
Sullivan GJ, Hay DC, Park I, Fletcher J, Hannoun Z, Payne CM, Dalgetty D, Black JR, Ross JA, Samuel K, Wang G, Daley GQ, Lee J, Church GM, Forbes SJ, Iredale JP, Wilmut I. Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology 2009, 51: 329-335. PMID: 19877180, PMCID: PMC2799548, DOI: 10.1002/hep.23335.Peer-Reviewed Original ResearchGeneration of induced pluripotent stem cells from human blood
Loh YH, Agarwal S, Park IH, Urbach A, Huo H, Heffner GC, Kim K, Miller JD, Ng K, Daley GQ. Generation of induced pluripotent stem cells from human blood. Blood 2009, 113: 5476-5479. PMID: 19299331, PMCID: PMC2689048, DOI: 10.1182/blood-2009-02-204800.Peer-Reviewed Original ResearchConceptsPluripotent stem cellsPluripotent cell-specific genesPatient-specific stem cellsTranscription factorsStem cellsHuman embryonic stem cellsPluripotency-associated transcription factorsEmbryonic stem cellsCell-specific genesInduced pluripotent stem cellsDNA methylation statusEctopic expressionHematopoietic lineagesRetroviral transductionMethylation statusSomatic mutationsHuman dermal fibroblastsHuman bloodDermal fibroblastsCellsHuman peripheral blood cellsExpressionPluripotencyPeripheral blood cellsLineages
2006
In vitro generation of germ cells from murine embryonic stem cells
West JA, Park IH, Daley GQ, Geijsen N. In vitro generation of germ cells from murine embryonic stem cells. Nature Protocols 2006, 1: 2026-2036. PMID: 17487192, DOI: 10.1038/nprot.2006.303.Peer-Reviewed Original ResearchConceptsPutative primordial germ cellsEmbryonic stem cellsMurine embryonic stem cellsGerm cellsPrimordial germ cellsGerm cell developmentEmbryoid body differentiationHaploid male gametesStem cellsImprint erasureEpigenetic phenomenaGamete formationHaploid cellsGamete developmentMature gametesMale gametesStages of differentiationDifferentiation systemBody differentiationGerm layersCell developmentAggregates of cellsSpontaneous differentiationTeratoma formationCell allocation