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
2021
Diverse epigenetic mechanisms maintain parental imprints within the embryonic and extraembryonic lineages
Andergassen D, Smith ZD, Kretzmer H, Rinn JL, Meissner A. Diverse epigenetic mechanisms maintain parental imprints within the embryonic and extraembryonic lineages. Developmental Cell 2021, 56: 2995-3005.e4. PMID: 34752748, PMCID: PMC9463566, DOI: 10.1016/j.devcel.2021.10.010.Peer-Reviewed Original ResearchConceptsX-chromosome inactivationGenomic imprintingEpigenetic mechanismsEpigenetic pathwaysIndependent gene clustersPolycomb group repressorsDiverse epigenetic mechanismsDistinct gene setsAllele-specific expressionH3K9 methyltransferase G9aAutosomal imprintingChromosomal scaleExtraembryonic lineagesParental imprintsPlacental lineagesGene clusterChromosome inactivationEutherian mammalsMethyltransferase G9aDNA methylationExtraembryonic ectodermGene setsSingle locusX chromosomeDistinct domains
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 ResearchConceptsMutant 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 cooperativityGastrulation
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
Genetic determinants and epigenetic effects of pioneer-factor occupancy
Donaghey J, Thakurela S, Charlton J, Chen JS, Smith ZD, Gu H, Pop R, Clement K, Stamenova EK, Karnik R, Kelley DR, Gifford CA, Cacchiarelli D, Rinn JL, Gnirke A, Ziller MJ, Meissner A. Genetic determinants and epigenetic effects of pioneer-factor occupancy. Nature Genetics 2018, 50: 250-258. PMID: 29358654, PMCID: PMC6517675, DOI: 10.1038/s41588-017-0034-3.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsBinding SitesCell LineageCells, CulturedComputational BiologyDNAEpigenesis, GeneticEpistasis, GeneticGATA4 Transcription FactorGene Expression RegulationGene Regulatory NetworksGenes, SwitchHEK293 CellsHep G2 CellsHepatocyte Nuclear Factor 3-betaHumansOctamer Transcription Factor-3Protein BindingTranscription FactorsConceptsCell typesAlternative cell typesGenomic occupancyDNA accessibilityPioneer factorsDNA replicationDNA methylationDNA sequencesEpigenetic effectsGene expressionDevelopmental transitionsMolecular componentsGenetic determinantsFOXA2TF activityGATA4Specific bindingExpressionSubsequent lossOccupancyEnrichmentMethylationLociLow enrichmentBinding
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 Research
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
2012
DNA Methylation Dynamics during In Vivo Differentiation of Blood and Skin Stem Cells
Bock C, Beerman I, Lien WH, Smith ZD, Gu H, Boyle P, Gnirke A, Fuchs E, Rossi DJ, Meissner A. DNA Methylation Dynamics during In Vivo Differentiation of Blood and Skin Stem Cells. Molecular Cell 2012, 47: 633-647. PMID: 22841485, PMCID: PMC3428428, DOI: 10.1016/j.molcel.2012.06.019.Peer-Reviewed Original ResearchConceptsDNA methylationHigh-resolution DNA methylation mapsVivo differentiationLineage-associated transcription factorsAdult stem cell differentiationDNA methylation mapsDNA methylation dynamicsGenome-scale dataCellular differentiation hierarchiesDNA methylation changesStem cellsStem cell differentiationAdult stem cellsTranscription factor activationSkin stem cellsMethylation mapsGenomic distributionMethylation dynamicsDifferentiation hierarchyEpigenetic regulationBlood lineagesTranscription factorsTissue homeostasisMethylation changesGene expression
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