2020
Epigenetic regulator function through mouse gastrulation
Grosswendt S, Kretzmer H, Smith ZD, Kumar AS, Hetzel S, Wittler L, Klages S, Timmermann B, Mukherji S, Meissner A. Epigenetic regulator function through mouse gastrulation. Nature 2020, 584: 102-108. PMID: 32728215, PMCID: PMC7415732, DOI: 10.1038/s41586-020-2552-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineageEpigenesis, GeneticFemaleGastrulaGastrulationGene Expression Regulation, DevelopmentalMaleMiceMutationPolycomb Repressive Complex 1Polycomb Repressive Complex 2Single-Cell AnalysisTranscription, GeneticConceptsMutant phenotypePolycomb Repressive Complex 1Single-cell RNA sequencingComplex mutant phenotypesSingle totipotent cellRepressive Complex 1Mutant mouse embryosSpecific transcription factorsMouse gastrulationTranscriptional informationEpigenetic machineryHistone residuesMolecular functionsCellular diversityTotipotent cellsTranscriptional changesTranscription factorsEssential regulatorRNA sequencingDevelopmental roleMouse embryosGenetic templatesRegulator functionSubstantial cooperativityGastrulationTETs compete with DNMT3 activity in pluripotent cells at thousands of methylated somatic enhancers
Charlton J, Jung EJ, Mattei AL, Bailly N, Liao J, Martin EJ, Giesselmann P, Brändl B, Stamenova EK, Müller FJ, Kiskinis E, Gnirke A, Smith ZD, Meissner A. TETs compete with DNMT3 activity in pluripotent cells at thousands of methylated somatic enhancers. Nature Genetics 2020, 52: 819-827. PMID: 32514123, PMCID: PMC7415576, DOI: 10.1038/s41588-020-0639-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell LineDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3AEmbryonic Stem CellsEnhancer Elements, GeneticEpigenesis, GeneticGene Expression Regulation, DevelopmentalGerm LayersHumansMiceMice, KnockoutMixed Function OxygenasesPluripotent Stem CellsProto-Oncogene ProteinsConceptsPluripotent cellsHuman embryonic stem cell linesEmbryonic stem cell linesDNA methylation landscapeEpiblast stem cellsStem cell linesGlobal methylation levelsMethylation landscapeMouse ESCsMammalian cellsRegulatory sequencesDNA methylationSomatic tissuesNegative regulatorTET expressionMethylation levelsDynamic locusStem cellsCell linesLociDemethylationRegulatorEnhancerCellsTet
2019
Loss 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 differentiationMolecular recording of mammalian embryogenesis
Chan MM, Smith ZD, Grosswendt S, Kretzmer H, Norman TM, Adamson B, Jost M, Quinn JJ, Yang D, Jones MG, Khodaverdian A, Yosef N, Meissner A, Weissman JS. Molecular recording of mammalian embryogenesis. Nature 2019, 570: 77-82. PMID: 31086336, PMCID: PMC7229772, DOI: 10.1038/s41586-019-1184-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell LineageEmbryo, MammalianEmbryonic DevelopmentEmbryonic Stem CellsEndodermFemaleFertilizationGastrulationGene Expression Regulation, DevelopmentalMaleMiceOrgan SpecificityPhenotypeSequence Analysis, RNASingle-Cell AnalysisConceptsCell fate mapsComplex multicellular organismsSingle totipotent cellSingle-cell readoutsSingle-cell RNA sequencing profilesEmbryonic progenitor cellsMulticellular organismsMammalian embryogenesisTranscriptional convergenceRNA sequencing profilesTotipotent cellsInternal gestationMammalian systemsAsymmetric partitioningMolecular recordersEndodermal cellsLineage tracerDevelopmental processesLineage informationMolecular recordingSequencing profilesEmbryonic originDifferent tissue typesProgenitor cellsTissue types
2017
Epigenetic restriction of extraembryonic lineages mirrors the somatic transition to cancer
Smith ZD, Shi J, Gu H, Donaghey J, Clement K, Cacchiarelli D, Gnirke A, Michor F, Meissner A. Epigenetic restriction of extraembryonic lineages mirrors the somatic transition to cancer. Nature 2017, 549: 543-547. PMID: 28959968, PMCID: PMC5789792, DOI: 10.1038/nature23891.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlastocystCell LineageCpG IslandsDNA MethylationEctodermEpigenesis, GeneticFemaleGene Expression Regulation, DevelopmentalGene Expression Regulation, NeoplasticGerm LayersHumansMaleMiceNeoplasmsPlacentaPregnancyPromoter Regions, Genetic
2014
DNA methylation dynamics of the human preimplantation embryo
Smith ZD, Chan MM, Humm KC, Karnik R, Mekhoubad S, Regev A, Eggan K, Meissner A. DNA methylation dynamics of the human preimplantation embryo. Nature 2014, 511: 611-615. PMID: 25079558, PMCID: PMC4178976, DOI: 10.1038/nature13581.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlastocystCell LineCpG IslandsDNADNA MethylationEmbryonic Stem CellsFemaleGene Expression Regulation, DevelopmentalHumansMaleMiceMice, Inbred C57BLConceptsGenome-scale DNA methylationMaternal-specific methylationDNA methylation dynamicsTransposable element activityEmbryonic stem cell derivationStem cell derivationEarly human embryogenesisHuman preimplantation embryosMethylation dynamicsDNA methylationHuman embryogenesisElement activityPreimplantation embryosCell derivationUnique modeMethylationEmbryogenesisMouse modelEmbryosRegulationExpressionIn 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
2013
Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging
Beerman I, Bock C, Garrison BS, Smith ZD, Gu H, Meissner A, Rossi DJ. Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging. Cell Stem Cell 2013, 12: 413-425. PMID: 23415915, DOI: 10.1016/j.stem.2013.01.017.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationCellular SenescenceDNA MethylationDNA ReplicationGene Expression Regulation, DevelopmentalHematopoiesisHematopoietic Stem CellsMaleMiceMice, Inbred C57BLModels, BiologicalPolycomb Repressive Complex 2TelomereConceptsDNA methylationHSC declineHematopoietic stem cell agingPolycomb repressive complex 2DNA methylation landscapeStem cell agingStem cell declineRepressive complex 2Global DNA methylationSite-specific alterationsHematopoietic lineage potentialMethylation landscapeDNA methylomeGenomic regionsLineage potentialEpigenomic alterationsDNA hypermethylationReplicative limitCell agingDownstream progenitorsFunctional analysisFunctional potentialMethylationProliferation of HSCsGenesDNA methylation: roles in mammalian development
Smith ZD, Meissner A. DNA methylation: roles in mammalian development. Nature Reviews Genetics 2013, 14: 204-220. PMID: 23400093, DOI: 10.1038/nrg3354.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCpG IslandsDNA MethylationEmbryonic Stem CellsEpigenesis, GeneticGene Expression RegulationGene Expression Regulation, DevelopmentalGenomic ImprintingGerm CellsHematopoiesisHumansMammalsConceptsEmbryonic stem cellsDNA methylationMammalian developmentPaternal genomeEmbryonic lineagesEpigenetic mechanismsPrimordial germ cell specificationDNA methylation erasureDNA methylation functionsKey PointsDNA methylationGerm cell specificationGermline-specific genesGlobal nuclear organizationSimilar epigenetic mechanismsTranscription factor bindingStem cellsPre-implantation stagesAdult stem cellsCpG island methylationMethylation erasureHeritable memoryMethylation functionsCell specificationCpG densityLineage specification
2011
Lung Stem Cell Self-Renewal Relies on BMI1-Dependent Control of Expression at Imprinted Loci
Zacharek SJ, Fillmore CM, Lau AN, Gludish DW, Chou A, Ho JW, Zamponi R, Gazit R, Bock C, Jäger N, Smith ZD, Kim TM, Saunders AH, Wong J, Lee JH, Roach RR, Rossi DJ, Meissner A, Gimelbrant AA, Park PJ, Kim CF. Lung Stem Cell Self-Renewal Relies on BMI1-Dependent Control of Expression at Imprinted Loci. Cell Stem Cell 2011, 9: 272-281. PMID: 21885022, PMCID: PMC3167236, DOI: 10.1016/j.stem.2011.07.007.Peer-Reviewed Original ResearchMeSH KeywordsAdult Stem CellsAnimalsCell SurvivalCells, CulturedCyclin-Dependent Kinase Inhibitor p16Gene Expression ProfilingGene Expression Regulation, DevelopmentalGenes, p16Genetic LociGenomic ImprintingLungMiceMice, Mutant StrainsNuclear ProteinsPolycomb Repressive Complex 1Proto-Oncogene ProteinsRegenerationRepressor ProteinsRNA, Small InterferingS-Phase Kinase-Associated ProteinsConceptsImprinted lociBronchioalveolar stem cellsStem cellsAdult tissue-specific stem cellsTissue-specific stem cellsLung epithelial stem cellsSelf-renewal defectLung epithelial cell injuryLung stem cellsDevelopmental processesEpithelial stem cellsExpression of p57Bmi1 knockout miceLung cellsGenesAdult cellsLociExpressionCellsAllelesRegulationKnockout miceEpithelial cell injuryFundamental questionsCDKN1C