2022
Hijacking of transcriptional condensates by endogenous retroviruses
Asimi V, Sampath Kumar A, Niskanen H, Riemenschneider C, Hetzel S, Naderi J, Fasching N, Popitsch N, Du M, Kretzmer H, Smith ZD, Weigert R, Walther M, Mamde S, Meierhofer D, Wittler L, Buschow R, Timmermann B, Cisse II, Ameres SL, Meissner A, Hnisz D. Hijacking of transcriptional condensates by endogenous retroviruses. Nature Genetics 2022, 54: 1238-1247. PMID: 35864192, PMCID: PMC9355880, DOI: 10.1038/s41588-022-01132-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEmbryonic Stem CellsEndogenous RetrovirusesHeterochromatinMammalsMiceNuclear BodiesRetroelementsConceptsTranscriptional condensatesEndogenous retrovirusesMurine embryonic stem cellsSingle-cell RNA-seq analysisKnockout mouse embryosRNA-seq analysisEmbryonic stem cellsMost endogenous retrovirusesERV RNAsPhase-separated dropletsNascent RNAPluripotency genesPluripotent lineageRNA polymeraseTranscription factorsReconstitution systemTriggers dissociationERV lociMouse embryosMediator coactivatorSelective degradationDisease contextsStem cellsRNASpecific depletion
2020
TETs 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
Molecular 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 ResearchConceptsCell 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
2018
Targets and genomic constraints of ectopic Dnmt3b expression
Zhang Y, Charlton J, Karnik R, Beerman I, Smith ZD, Gu H, Boyle P, Mi X, Clement K, Pop R, Gnirke A, Rossi DJ, Meissner A. Targets and genomic constraints of ectopic Dnmt3b expression. ELife 2018, 7: e40757. PMID: 30468428, PMCID: PMC6251628, DOI: 10.7554/elife.40757.Peer-Reviewed Original ResearchConceptsDNA methylationCpG islandsDe novo DNA methyltransferase DNMT3BCertain CpG islandsDNA methyltransferase DNMT3BGenome-wide dataCpG island hypermethylationDifferent cell typesMammalian genomesChromatin landscapeGenomic constraintsTranscriptional statesCancer methylomeMethyltransferase DNMT3BBisulfite sequencingGenomic targetsIsland hypermethylationResponsible enzymeDNMT3B expressionAberrant methylationDNMT3BMethylationCell typesH3K27me3Essential roleGlobal delay in nascent strand DNA methylation
Charlton J, Downing TL, Smith ZD, Gu H, Clement K, Pop R, Akopian V, Klages S, Santos DP, Tsankov AM, Timmermann B, Ziller MJ, Kiskinis E, Gnirke A, Meissner A. Global delay in nascent strand DNA methylation. Nature Structural & Molecular Biology 2018, 25: 327-332. PMID: 29531288, PMCID: PMC5889353, DOI: 10.1038/s41594-018-0046-4.Peer-Reviewed Original ResearchMeSH KeywordsCell CycleCell ProliferationCpG IslandsCytosineDNADNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3ADNA ReplicationEmbryonic Stem CellsEpigenesis, GeneticGene Expression RegulationGenome, HumanHCT116 CellsHumansMaleMethylationMitosisMotor NeuronsNeoplasmsSequence Analysis, RNATranscription FactorsConceptsCytosine methylationCpG methylationGenome-wide bisulfite sequencingCis-regulatory elementsEmbryonic stem cellsCancer cell line HCT116Cell cycle arrestEpigenetic informationMammalian developmentGene regulationMitotic transmissionEpigenetic heterogeneityEpigenetic roleBisulfite sequencingCell line HCT116DNA methylationHuman cellsMethylationHeterogeneous methylationStem cellsCellsBrdU labelingPronounced lagGlobal reductionImmunoprecipitation
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 ResearchConceptsGenome-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
DNA 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 ResearchConceptsEmbryonic 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
2012
Epigenomics and chromatin dynamics
Akopian V, Chan MM, Clement K, Galonska C, Gifford CA, Lehtola E, Liao J, Samavarchi-Tehrani P, Sindhu C, Smith ZD, Tsankov AM, Webster J, Zhang Y, Ziller MJ, Meissner A. Epigenomics and chromatin dynamics. Genome Biology 2012, 13: 313. PMID: 22364154, PMCID: PMC3334565, DOI: 10.1186/gb-2012-13-2-313.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsCell DifferentiationCell LineDNA MethylationEmbryonic Stem CellsGene Expression ProfilingHumansInduced Pluripotent Stem CellsConceptsPluripotent 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
Dynamic single-cell imaging of direct reprogramming reveals an early specifying event
Smith ZD, Nachman I, Regev A, Meissner A. Dynamic single-cell imaging of direct reprogramming reveals an early specifying event. Nature Biotechnology 2010, 28: 521-526. PMID: 20436460, PMCID: PMC2908494, DOI: 10.1038/nbt.1632.Peer-Reviewed Original Research