2023
Self-patterning of human stem cells into post-implantation lineages
Pedroza M, Gassaloglu S, Dias N, Zhong L, Hou T, Kretzmer H, Smith Z, Sozen B. Self-patterning of human stem cells into post-implantation lineages. Nature 2023, 622: 574-583. PMID: 37369348, PMCID: PMC10584676, DOI: 10.1038/s41586-023-06354-4.Peer-Reviewed Original ResearchConceptsStem cellsPlacental cell typesPost-implantation embryonic developmentHuman pluripotent stem cellsPluripotent stem cellsHuman embryonic developmentEmbryonic developmentHuman stem cellsCongenital pathologyPost-implantation epiblastDiverse cell statesSingle-cell transcriptomicsAmniotic ectodermExtra-embryonic endodermSpontaneous differentiationSignaling hubThree-dimensional structureSecreted modulatorsCell types
2019
Differential regulation of OCT4 targets facilitates reacquisition of pluripotency
Thakurela S, Sindhu C, Yurkovsky E, Riemenschneider C, Smith ZD, Nachman I, Meissner A. Differential regulation of OCT4 targets facilitates reacquisition of pluripotency. Nature Communications 2019, 10: 4444. PMID: 31570708, PMCID: PMC6768871, DOI: 10.1038/s41467-019-11741-5.Peer-Reviewed Original ResearchConceptsEctopic transcription factorsReacquisition of pluripotencySomatic cell reprogrammingCis-regulatory elementsTranscription factor expressionExact molecular mechanismsOCT4 targetsPluripotent stem cellsPluripotency inductionCell reprogrammingTranscription factorsSomatic cellsMolecular mechanismsDifferential regulationPluripotencyStem cellsVivo differentiationPrimary targetCellsFactor expressionFinal stepExperimental systemReprogrammingTargetDifferentiationLoss of DNA methyltransferase activity in primed human ES cells triggers increased cell-cell variability and transcriptional repression
Tsankov AM, Wadsworth MH, Akopian V, Charlton J, Allon SJ, Arczewska A, Mead BE, Drake RS, Smith ZD, Mikkelsen TS, Shalek AK, Meissner A. Loss of DNA methyltransferase activity in primed human ES cells triggers increased cell-cell variability and transcriptional repression. Development 2019, 146: dev174722. PMID: 31515224, PMCID: PMC6803377, DOI: 10.1242/dev.174722.Peer-Reviewed Original ResearchMeSH KeywordsCell CycleCell DifferentiationDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3AEnhancer Elements, GeneticEntropyGene Expression Regulation, DevelopmentalHuman Embryonic Stem CellsHumansMaleRepressor ProteinsRNA, MessengerTranscription, GeneticConceptsGlobal methylation levelsTranscriptional repressionSingle-cell RNA-sequencing dataMethylation levelsNew cell fatesMaintenance of pluripotencyHuman embryonic stem cellsMethylation of cytosineRNA-sequencing dataCell-cell variabilityStem cellsEmbryonic stem cellsHuman pluripotent stem cellsDNA methyltransferase activityMRNA expression dataPluripotent stem cellsTranscriptional variabilityMethyltransferases Dnmt3aCell fateEpigenetic regulatorsMethyltransferase DNMT3AExtrinsic signalsHigh-resolution viewMethyltransferase activityProper differentiation
2016
Molecular features of cellular reprogramming and development
Smith ZD, Sindhu C, Meissner A. Molecular features of cellular reprogramming and development. Nature Reviews Molecular Cell Biology 2016, 17: 139-154. PMID: 26883001, DOI: 10.1038/nrm.2016.6.Peer-Reviewed Original ResearchConceptsKrüppel-like factor 4Pluripotent stateSRY-box 2Somatic cellsDirect reprogrammingInduced pluripotent stem cell generationDifferentiated cellsPluripotent stem cell generationCis-regulatory elementsStem cell generationAdditional molecular featuresMolecular featuresPluripotent stem cellsChromatin remodellersBivalent chromatinEpigenetic barriersDevelopmental genesCellular identityCellular reprogrammingGenetic modulesEpigenetic regulationCompact chromatinTranscriptional inductionEpigenetic repressorEpigenetic modifiers
2015
Epigenetic predisposition to reprogramming fates in somatic cells
Pour M, Pilzer I, Rosner R, Smith ZD, Meissner A, Nachman I. Epigenetic predisposition to reprogramming fates in somatic cells. EMBO Reports 2015, 16: 370-378. PMID: 25600117, PMCID: PMC4364876, DOI: 10.15252/embr.201439264.Peer-Reviewed Original ResearchConceptsSomatic cellsFactor inductionLive-cell imagingPluripotent stem cellsEpigenetic stateCell identitySuccessful reprogrammingEpigenetic heterogeneityDaughter cellsSister cellsCell lineagesCellular responsesLineagesEZH2 inhibitorsLow-efficiency processColony formationStem cellsEpigenetic predispositionReprogramPopulation levelCellsNovel statistical approachSomatic populationInductionFate
2014
In Vivo and In Vitro Dynamics of Undifferentiated Embryonic Cell Transcription Factor 1
Galonska C, Smith ZD, Meissner A. In Vivo and In Vitro Dynamics of Undifferentiated Embryonic Cell Transcription Factor 1. Stem Cell Reports 2014, 2: 245-252. PMID: 24672748, PMCID: PMC3964277, DOI: 10.1016/j.stemcr.2014.01.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersCell DifferentiationCell LineCellular ReprogrammingChromosomal Proteins, Non-HistoneDNAEmbryo, MammalianEmbryonic Stem CellsGene ExpressionGene Expression Regulation, DevelopmentalGene OrderGenes, ReporterGenetic VectorsMicePluripotent Stem CellsProtein BindingTrans-ActivatorsTranscription FactorsConceptsEmbryonic cell transcription factor 1Transcription factor 1Reporter linesDiverse rolesUndifferentiated embryonic cell transcription factor 1Factor 1Stem cell conditionsPluripotent stem cellsTargeted locusTranscription factorsDynamic regulationGerm layersBiotinylation systemUTF1Stem cellsCell conditionsPluripotencyGermlineLociRegulatorReporterBetter understandingRegulationLinesMajor interest
2011
Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines
Bock C, Kiskinis E, Verstappen G, Gu H, Boulting G, Smith ZD, Ziller M, Croft GF, Amoroso MW, Oakley DH, Gnirke A, Eggan K, Meissner A. Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines. Cell 2011, 144: 439-452. PMID: 21295703, PMCID: PMC3063454, DOI: 10.1016/j.cell.2010.12.032.Peer-Reviewed Original ResearchConceptsPluripotent cell linesEmbryonic stemPluripotent stem cellsCell linesDisease-relevant cell typesHuman iPS cell linesStem cellsReference mapHuman pluripotent stem cellsHuman embryonic stemIPS cell linesDifferentiation propensityDNA methylationIndividual cell linesHigh-throughput characterizationTranscriptional similarityGene expressionIPS cellsCell typesDifferentiation efficiencyDevelopmental potentialBiomedical researchComprehensive characterizationSpecific differencesCells
2010
Highly Efficient Reprogramming to Pluripotency and Directed Differentiation of Human Cells with Synthetic Modified mRNA
Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ. Highly Efficient Reprogramming to Pluripotency and Directed Differentiation of Human Cells with Synthetic Modified mRNA. Cell Stem Cell 2010, 7: 618-630. PMID: 20888316, PMCID: PMC3656821, DOI: 10.1016/j.stem.2010.08.012.Peer-Reviewed Original ResearchConceptsInduced pluripotent stem cellsPluripotent stem cellsCell fateMultiple human cell typesSomatic cell reprogrammingCell typesUseful cell typesStem cellsHuman cell typesPatient-specific induced pluripotent stem cellsCell reprogrammingCellular reprogrammingInnate antiviral responseDirected DifferentiationIPSC derivationHuman cellsMyogenic cellsSynthetic mRNAAntiviral responseDisease modelingReprogrammingModified mRNARegenerative medicineFateMRNA