2025
From genes to geometry: Controlling embryo models by programming genomic activation
McNamara H, Sozen B. From genes to geometry: Controlling embryo models by programming genomic activation. Cell Stem Cell 2025, 32: 857-858. PMID: 40480203, DOI: 10.1016/j.stem.2025.04.013.Peer-Reviewed Original Research
2023
DOT1L bridges transcription and heterochromatin formation at mammalian pericentromeres
Malla A, Yu H, Farris D, Kadimi S, Lam T, Cox A, Smith Z, Lesch B. DOT1L bridges transcription and heterochromatin formation at mammalian pericentromeres. EMBO Reports 2023, 24: embr202256492. PMID: 37317657, PMCID: PMC10398668, DOI: 10.15252/embr.202256492.Peer-Reviewed Original ResearchConceptsMouse embryonic stem cellsBurst of transcriptionMajor satellite repeatsLong-term silencingRepetitive DNA elementsEmbryonic stem cellsSatellite transcriptionHeterochromatin stabilityHeterochromatin formationHeterochromatin structureChromatin stateSatellite repeatsGenome stabilityGenome integrityPericentromeric repeatsPericentromeric heterochromatinGenome featuresDNA elementsHistone H3Transcriptional activationHistone methyltransferaseRepetitive elementsDOT1L lossRepeat elementsTranscript production
2019
Self-Organization of Mouse Stem Cells into an Extended Potential Blastoid
Sozen B, Cox A, De Jonghe J, Bao M, Hollfelder F, Glover D, Zernicka-Goetz M. Self-Organization of Mouse Stem Cells into an Extended Potential Blastoid. Developmental Cell 2019, 51: 698-712.e8. PMID: 31846649, PMCID: PMC10291877, DOI: 10.1016/j.devcel.2019.11.014.Peer-Reviewed Original ResearchConceptsBlastocyst-like structuresStem cellsEmbryonic stem cellsEmbryonic-abembryonic axisTrophoblast stem cellsExtra-embryonic primitive endodermExtra-embryonic lineagesPrimitive endoderm differentiationMouse stem cellsTranscriptome profiling analysisEpiblast lineageMouse embryonic stem cellsMammalian blastocystCell lineagesPluripotent epiblastPluripotency conditionsFuture embryoPrimitive endodermEndoderm differentiationLineagesCellsHistone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally
Huang H, Weng H, Zhou K, Wu T, Zhao BS, Sun M, Chen Z, Deng X, Xiao G, Auer F, Klemm L, Wu H, Zuo Z, Qin X, Dong Y, Zhou Y, Qin H, Tao S, Du J, Liu J, Lu Z, Yin H, Mesquita A, Yuan CL, Hu YC, Sun W, Su R, Dong L, Shen C, Li C, Qing Y, Jiang X, Wu X, Sun M, Guan JL, Qu L, Wei M, Müschen M, Huang G, He C, Yang J, Chen J. Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally. Nature 2019, 567: 414-419. PMID: 30867593, PMCID: PMC6438714, DOI: 10.1038/s41586-019-1016-7.Peer-Reviewed Original ResearchConceptsM6A methyltransferase complexHistone H3 trimethylationH3 trimethylationHistone modificationsImportant post-transcriptional mechanismMouse embryonic stem cellsGene expression regulationRNA polymerase IIPrevalent internal modificationPost-transcriptional mechanismsEmbryonic stem cellsN6-methyladenosine (m<sup>6</sup>A) mRNA modificationM6A depositionTranscription elongationNascent RNAMethyltransferase complexPolymerase IIExpression regulationGene expression1RNA methylationMRNA modificationMETTL14 knockdownH3K36me3M6A modificationCell stemness
2018
In vitro generation of mouse polarized embryo-like structures from embryonic and trophoblast stem cells
Harrison S, Sozen B, Zernicka-Goetz M. In vitro generation of mouse polarized embryo-like structures from embryonic and trophoblast stem cells. Nature Protocols 2018, 13: 1586-1602. PMID: 29988106, DOI: 10.1038/s41596-018-0005-x.Peer-Reviewed Original ResearchConceptsTrophoblast stem cellsEmbryonic stem cellsMouse embryonic stem cellsExtra-embryonic tissuesStem cellsGerm-layer specificationEmbryos in vitroExtracellular matrixStem cell typesIn vitro generationPost-implantation developmentEmbryo-like structuresEarly embryos in vitroBody planMammalian developmentMammalian embryogenesisTissue in vitroEarly embryosEmbryonic tissues in vitroAggregates of embryonic stem cellsCell numberCo-CultureEmbryonic architectureCell typesCulture conditionsA Regulatory Circuitry Between Gria2, miR-409, and miR-495 Is Affected by ALS FUS Mutation in ESC-Derived Motor Neurons
Capauto D, Colantoni A, Lu L, Santini T, Peruzzi G, Biscarini S, Morlando M, Shneider NA, Caffarelli E, Laneve P, Bozzoni I. A Regulatory Circuitry Between Gria2, miR-409, and miR-495 Is Affected by ALS FUS Mutation in ESC-Derived Motor Neurons. Molecular Neurobiology 2018, 55: 7635-7651. PMID: 29430619, PMCID: PMC6132778, DOI: 10.1007/s12035-018-0884-4.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisMotor neuronsFUS mutationsMouse embryonic stem cellsPathogenesis of ALSMiRNA-dependent regulationCorresponding mRNA targetsNeuron-specific RNATypes of RNAEmbryonic stem cellsCross talkGlutamate α-aminoIsoxazole propionic acidDisease-associated mutationsMolecular cross talkDisturbance of Ca2Juvenile-onset formMiRNA repressionRegulatory circuitryTranscriptome profilingMRNA targetsMultifunctional proteinLong RNAsMN degenerationExcitatory neurotransmission
2017
Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro
Harrison S, Sozen B, Christodoulou N, Kyprianou C, Zernicka-Goetz M. Assembly of embryonic and extraembryonic stem cells to mimic embryogenesis in vitro. Science 2017, 356 PMID: 28254784, DOI: 10.1126/science.aal1810.Peer-Reviewed Original ResearchConceptsTrophoblast stem cellsStem cellsEmbryonic stem cellsGenetically modified stem cellsExtraembryonic stem cellsGerm cell markersPrimordial germ cell markersStem cell typesCell typesExpression of mesodermCell markersNatural embryoDevelopmental potentialExtraembryonic tissuesMouse embryonic stem cellsMammalian embryogenesisBMP signalingResponse to WntCellsCross-talkThree-dimensional scaffoldsEmbryosSelf-assembly in vitroCoordinated morphogenesis
2016
DNA methylation on N6-adenine in mammalian embryonic stem cells
Wu TP, Wang T, Seetin MG, Lai Y, Zhu S, Lin K, Liu Y, Byrum SD, Mackintosh SG, Zhong M, Tackett A, Wang G, Hon LS, Fang G, Swenberg JA, Xiao AZ. DNA methylation on N6-adenine in mammalian embryonic stem cells. Nature 2016, 532: 329-333. PMID: 27027282, PMCID: PMC4977844, DOI: 10.1038/nature17640.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAlkB Homolog 1, Histone H2a DioxygenaseAnimalsCell DifferentiationDNA MethylationDNA Transposable ElementsDNA-(Apurinic or Apyrimidinic Site) LyaseEnhancer Elements, GeneticEpigenesis, GeneticEvolution, MolecularGene SilencingLong Interspersed Nucleotide ElementsMammalsMiceMouse Embryonic Stem CellsUp-RegulationX ChromosomeConceptsLINE-1 transposonsEmbryonic stem cellsN6-methyladenineMammalian genomesEpigenetic silencingDNA methylationX chromosomeMammalian embryonic stem cellsEmbryonic stem cell differentiationMouse embryonic stem cellsStem cellsStem cell differentiationMammalian evolutionTranscriptional silencingEvolutionary ageGene activationDNA modificationsL1 elementsCell differentiationSilencingTransposonN6-adenineGenomeActivation signalsChromosomesDivergence and rewiring of regulatory networks for neural development between human and other species
Wang P, Zhao D, Rockowitz S, Zheng D. Divergence and rewiring of regulatory networks for neural development between human and other species. Neurogenesis 2016, 3: e1231495. PMID: 27900343, PMCID: PMC5111580, DOI: 10.1080/23262133.2016.1231495.Peer-Reviewed Original ResearchRegulatory networksTranscription factorsNeural developmentMouse embryonic stem cellsREST-binding sitesGene regulatory networksCritical transcriptional regulatorREST/NRSFEmbryonic stem cellsTranscriptional regulatorsEpigenetic regulationGenomic regionsGenetic controlMammalian speciesFunctional implicationsGenesStem cellsRest regulationsSpeciesBinding eventsFunctional featuresCritical roleRegulationBrain developmentRecent analysis
2015
Analysis of dynamic changes in retinoid-induced transcription and epigenetic profiles of murine Hox clusters in ES cells
De Kumar B, Parrish M, Slaughter B, Unruh J, Gogol M, Seidel C, Paulson A, Li H, Gaudenz K, Peak A, McDowell W, Fleharty B, Ahn Y, Lin C, Smith E, Shilatifard A, Krumlauf R. Analysis of dynamic changes in retinoid-induced transcription and epigenetic profiles of murine Hox clusters in ES cells. Genome Research 2015, 25: 1229-1243. PMID: 26025802, PMCID: PMC4510006, DOI: 10.1101/gr.184978.114.Peer-Reviewed Original ResearchConceptsChromatin modificationsHomeotic clustersHox genesES cellsClustered Hox genesHomeotic gene transcriptionMouse embryonic stem cellsNoncoding RNA genesRetinoid-induced transcriptionGenome-wide approachesCis-regulatory elementsEmbryonic stem cellsTranscription stateChromatin marksHOXB clusterNoncoding genesRNA genesSegmental identityActive transcriptionNoncoding RNAsTranscription factorsEpigenetic profilesGene transcriptionEpigenetic changesBody axis
2014
Using Native Chromatin Immunoprecipitation to Interrogate Histone Variant Protein Deposition in Embryonic Stem Cells
Tseng Z, Wu T, Liu Y, Zhong M, Xiao A. Using Native Chromatin Immunoprecipitation to Interrogate Histone Variant Protein Deposition in Embryonic Stem Cells. Methods In Molecular Biology 2014, 1176: 11-22. PMID: 25030915, DOI: 10.1007/978-1-4939-0992-6_2.Peer-Reviewed Original ResearchConceptsNative chromatin immunoprecipitationHigh-throughput sequencingEmbryonic stem cellsChromatin immunoprecipitationHistone variantsMouse embryonic stem cellsGenome-wide localizationChromatin-associated factorsStem cellsProtein of interestMassive parallel sequencingHistone modificationsChromatin regionsChromatin pelletEpigenetic techniquesDNA fragmentsParallel sequencingImmunoprecipitationLibrary constructionSequencingEnzymatic digestionProtein depositionCellsH2A.XSpecific antibodies
2009
Hematopoietic Development From Human Induced Pluripotent Stem Cells.
Grauer M, Konantz M, Niebuhr N, Kanz L, Park I, Daley G, Lengerke C. Hematopoietic Development From Human Induced Pluripotent Stem Cells. Blood 2009, 114: 2530. DOI: 10.1182/blood.v114.22.2530.2530.Peer-Reviewed Original ResearchMouse embryonic stem cellsEmbryonic stem cellsInduced pluripotent stem cellsPluripotent stem cellsHuman embryonic stem cellsHematopoietic stem cellsHuman induced pluripotent stem cellsHuman iPS cellsIPS cellsCdx genesHematopoietic developmentBlood lineagesStem cellsBlood formationEmbryonic blood formationGenetic modificationHuman developmental hematopoiesisDifferentiated somatic cellsHuman pluripotent stem cell linesStem cell linesIrradiated adult micePluripotent stem cell lineDevelopmental hematopoiesisHematopoietic genesHox genesHematopoietic Development from Human Induced Pluripotent Stem Cells
Lengerke C, Grauer M, Niebuhr NI, Riedt T, Kanz L, Park I, Daley GQ. Hematopoietic Development from Human Induced Pluripotent Stem Cells. Annals Of The New York Academy Of Sciences 2009, 1176: 219-227. PMID: 19796250, PMCID: PMC2849804, DOI: 10.1111/j.1749-6632.2009.04606.x.Peer-Reviewed Original ResearchConceptsEmbryonic stem cellsMouse embryonic stem cellsPluripotent stem cellsHematopoietic developmentInduced pluripotent stem cellsHuman induced pluripotent stem cellsHematopoietic stem cellsStem cellsDifferentiated somatic cellsHuman embryonic stem cellsHuman hematopoietic developmentStem cell linesGene expression dataIrradiated adult miceHox genesPluripotent stateBlood lineagesSomatic cellsEctopic expressionCombinatorial overexpressionExpression dataBlood formationIPS cellsColony activityMultilineage reconstitution
2008
Multimodal evaluation of in vivo magnetic resonance imaging of myocardial restoration by mouse embryonic stem cells
Hendry S, van der Bogt K, Sheikh A, Arai T, Dylla S, Drukker M, McConnell M, Kutschka I, Hoyt G, Cao F, Weissman I, Connolly A, Pelletier M, Wu J, Robbins R, Yang P. Multimodal evaluation of in vivo magnetic resonance imaging of myocardial restoration by mouse embryonic stem cells. Journal Of Thoracic And Cardiovascular Surgery 2008, 136: 1028-1037.e1. PMID: 18954646, DOI: 10.1016/j.jtcvs.2007.12.053.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDisease Models, AnimalEmbryonic Stem CellsFemaleFibroblastsGraft RejectionGraft SurvivalImmunohistochemistryMagnetic Resonance ImagingMiceMice, SCIDMyocardial ContractionMyocardial InfarctionMyocytes, CardiacRandom AllocationReproducibility of ResultsSensitivity and SpecificityStem Cell TransplantationStroke VolumeVentricular RemodelingConceptsEmbryonic stem cellsMagnetic resonance imagingIn vivo magnetic resonance imagingMouse embryonic stem cellsStem cellsResonance imagingMyocardial restorationIn vivo pressure-volume loopsPolymerase chain reactionLeft ventricular ejection fractionBioluminescence imagingSCID-beige miceVentricular ejection fractionEmbryonic stem cell groupStem cell groupMouse embryonic fibroblastsChain reactionIn vivo bioluminescence imagingCoronary artery ligationAssessment of functional recoveryAntifibrotic genesAcute myocardial infarctionDiastolic functionEjection fractionCardiac phenotypeCftr gene targeting in mouse embryonic stem cells mediated by Small Fragment Homologous Replacement (SFHR).
Sangiuolo F, Scaldaferri ML, Filareto A, Spitalieri P, Guerra L, Favia M, Caroppo R, Mango R, Bruscia E, Gruenert DC, Casavola V, De Felici M, Novelli G. Cftr gene targeting in mouse embryonic stem cells mediated by Small Fragment Homologous Replacement (SFHR). Frontiers In Bioscience-Landmark 2008, 13: 2989-99. PMID: 17981772, PMCID: PMC3725395, DOI: 10.2741/2904.Peer-Reviewed Original ResearchConceptsSmall fragment homologous replacementES cellsSmall DNA fragmentsGene functionHomologous replacementEmbryonic stem cell genomeMouse embryonic stem cell genomeGenomic DNAMurine ES cellsTissue-specific gene functionEndogenous genomic DNAMouse embryonic stem cellsSpecific genomic lociStem cell genomeNormal gene functionCFTR-dependent chloride effluxEmbryonic stem cellsDifferent cell lineagesGene correctionGenomic lociGenomic sequencesCFTR locusCell genomeDifferent genesCell lineages
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