2022
Expression 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
2017
Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration
Xiang Y, Tanaka Y, Patterson B, Kang YJ, Govindaiah G, Roselaar N, Cakir B, Kim KY, Lombroso AP, Hwang SM, Zhong M, Stanley EG, Elefanty AG, Naegele JR, Lee SH, Weissman SM, Park IH. Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration. Cell Stem Cell 2017, 21: 383-398.e7. PMID: 28757360, PMCID: PMC5720381, DOI: 10.1016/j.stem.2017.07.007.Peer-Reviewed Original ResearchConceptsHuman brain developmentChromatin accessibility dynamicsTransposase-accessible chromatinHigh-throughput sequencing analysisRegion-specific organoidsHuman pluripotent stem cellsRNA sequencing profilingHuman interneuron migrationPluripotent stem cellsRelated lineagesBrain developmentAccessibility dynamicsBulk assaysInterneuron migrationLineage relationshipsOrganoid techniquesSequencing profilingSequencing analysisFunctional neuronsOrganoid developmentStem cellsCortical organoidsOrganoidsBrain organoidsMGE
2016
Single 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 factorsDnmt1 regulates the myogenic lineage specification of muscle stem cells
Liu R, Kim KY, Jung YW, Park IH. Dnmt1 regulates the myogenic lineage specification of muscle stem cells. Scientific Reports 2016, 6: 35355. PMID: 27752090, PMCID: PMC5082760, DOI: 10.1038/srep35355.Peer-Reviewed Original ResearchConceptsImportant epigenetic markKnockout mouse approachesDNA methylation patternsMuscle stem cellsDaughter DNA strandsDNMT1 regulationEpigenetic marksLineage specificationCellular identityDNA methylationMethylation patternsDNMT1 depletionMyogenic genesMyogenic differentiationLineage fidelityNegative regulatorGene expressionDNMT1Osteogenic lineageFunctional roleFunctional consequencesMouse approachDNA strandsId-1Stem cells
2013
Modelling human disease with pluripotent stem cells.
Siller R, Greenhough S, Park IH, Sullivan GJ. Modelling human disease with pluripotent stem cells. Current Gene Therapy 2013, 13: 99-110. PMID: 23444871, PMCID: PMC3785403, DOI: 10.2174/1566523211313020004.Peer-Reviewed Original ResearchConceptsPluripotent stem cellsStem cellsAffected cell typesCellular reprogrammingEndodermal lineagesPluripotent cellsHuman diseasesCell typesGenetic diseasesDisease phenotypeDisease mechanismsDisease modellingTissue of interestPatient tissuesCellsLimitless supplyReprogrammingLineagesRecent progressProgenyPhenotypeTissueTherapeutic interventionsHigh levelsCell technology
2011
Stage-specific signaling through TGFβ family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells
Nostro MC, Sarangi F, Ogawa S, Holtzinger A, Corneo B, Li X, Micallef SJ, Park IH, Basford C, Wheeler MB, Daley GQ, Elefanty AG, Stanley EG, Keller G. Stage-specific signaling through TGFβ family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells. Development 2011, 138: 861-871. PMID: 21270052, PMCID: PMC3035090, DOI: 10.1242/dev.055236.Peer-Reviewed Original ResearchConceptsHuman pluripotent stem cellsPluripotent stem cellsTGFβ family membersStem cellsPancreatic lineage cellsEndoderm fateEndoderm populationEndoderm inductionPancreatic specificationInsulin-expressing cellsBMP inhibitionPancreatic lineagePancreatic fateA SignalingInsulin-producing β-cellsGerm layersCanonical WntDevelopmental stagesActivin A signalingFamily membersLineage cellsWntInsulin expressionCell linesSpecific stages
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 Research