2024
X-linked deletion of Crossfirre, Firre, and Dxz4 in vivo uncovers diverse phenotypes and combinatorial effects on autosomes
Hasenbein T, Hoelzl S, Smith Z, Gerhardinger C, Gonner M, Aguilar-Pimentel A, Amarie O, Becker L, Calzada-Wack J, Dragano N, da Silva-Buttkus P, Garrett L, Hölter S, Kraiger M, Östereicher M, Rathkolb B, Sanz-Moreno A, Spielmann N, Wurst W, Gailus-Durner V, Fuchs H, Hrabě de Angelis M, Meissner A, Engelhardt S, Rinn J, Andergassen D. X-linked deletion of Crossfirre, Firre, and Dxz4 in vivo uncovers diverse phenotypes and combinatorial effects on autosomes. Nature Communications 2024, 15: 10631. PMID: 39638999, PMCID: PMC11621363, DOI: 10.1038/s41467-024-54673-5.Peer-Reviewed Original ResearchConceptsAutosomal gene regulationRegions genome-wideAllele-specific analysisSex-specific lociLoci in vivoX-linked genesRandom X-chromosome inactivationX-chromosome inactivationSex-specific phenotypesFirre locusGenome-wideIn vivo roleChromatin structureGene regulationX chromosomeEpigenetic featuresDXZ4Epigenetic profilesKnockout studiesLociDiverse phenotypesLncRNA FIRREFunctional roleCombinatorial effectsFIRRE
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
In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation
Andergassen D, Smith ZD, Lewandowski JP, Gerhardinger C, Meissner A, Rinn JL. In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation. ELife 2019, 8: e47214. PMID: 31738164, PMCID: PMC6860989, DOI: 10.7554/elife.47214.Peer-Reviewed Original ResearchConceptsX-chromosome inactivationAutosomal gene regulationGene regulationDouble deletionOrgan-specific mannerChromosome inactivationGene setsX chromosomeTranscriptional effectsExpression signaturesLociCell linesDeletionGenesRegulationVivo contributionRecent evidenceMegadomainsAutosomesFIRREMutantsChromosomesMain driversBiologySuperloopsMolecular 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
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
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 modelEmbryosRegulationExpression
2012
Mouse ooplasm confers context-specific reprogramming capacity
Chan MM, Smith ZD, Egli D, Regev A, Meissner A. Mouse ooplasm confers context-specific reprogramming capacity. Nature Genetics 2012, 44: 978-980. PMID: 22902786, PMCID: PMC3432711, DOI: 10.1038/ng.2382.Peer-Reviewed Original ResearchA unique regulatory phase of DNA methylation in the early mammalian embryo
Smith ZD, Chan MM, Mikkelsen TS, Gu H, Gnirke A, Regev A, Meissner A. A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature 2012, 484: 339-344. PMID: 22456710, PMCID: PMC3331945, DOI: 10.1038/nature10960.Peer-Reviewed Original ResearchConceptsDNA methylationGenome-scale DNA methylation mapsLong terminal repeat (LTR) retroelementsDNA methylation mapsBase-resolution mapsEarly mammalian embryoCpG island promotersBlastocyst stageMammalian embryogenesisMethylation mapsPaternal genomeMammalian embryosEpigenetic modificationsEarly embryosSomatic cellsGlobal hypomethylationSomatic patternMouse gametesElement 1MethylationEmbryosMethylation valuesRegulatory phaseGametesZygotes