2023
Modelling post-implantation human development to yolk sac blood emergence
Hislop J, Song Q, Keshavarz F. K, Alavi A, Schoenberger R, LeGraw R, Velazquez J, Mokhtari T, Taheri M, Rytel M, Chuva de Sousa Lopes S, Watkins S, Stolz D, Kiani S, Sozen B, Bar-Joseph Z, Ebrahimkhani M. Modelling post-implantation human development to yolk sac blood emergence. Nature 2023, 626: 367-376. PMID: 38092041, PMCID: PMC10849971, DOI: 10.1038/s41586-023-06914-8.Peer-Reviewed Original ResearchConceptsHuman embryosInduced pluripotent stem cellsLymphoid-like cellsStem cell modelPluripotent stem cellsPost-implantation stagesAmniotic cavityEarly post-implantation stagesHuman-based modelsStem cellsExtra-embryonic endodermHuman embryogenesisBlood formationDrug testingEarly haematopoiesisDisease modelsDisc morphologyHaematopoiesisEmbryonic tissuesCellular programmeCell modelPosterior domainShifting early embryology paradigms: Applications of stem cell-based embryo models in bioengineering
Abel A, Sozen B. Shifting early embryology paradigms: Applications of stem cell-based embryo models in bioengineering. Current Opinion In Genetics & Development 2023, 81: 102069. PMID: 37392541, PMCID: PMC10530566, DOI: 10.1016/j.gde.2023.102069.Peer-Reviewed Original ResearchSelf-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
2022
Carnegie in 4D? Stem-cell-based models of human embryo development
Sozen B, Conkar D, Veenvliet J. Carnegie in 4D? Stem-cell-based models of human embryo development. Seminars In Cell And Developmental Biology 2022, 131: 44-57. PMID: 35701286, DOI: 10.1016/j.semcdb.2022.05.023.Peer-Reviewed Original ResearchConceptsEmbryo developmentMouse in vitro modelsHuman embryo developmentHuman pluripotent stem cellsPluripotent stem cellsModels of embryo developmentHuman developmentInvestigation of embryogenesisHuman embryosStem cellsPrimate embryosIn vitro approachesIn vitroMammalian embryogenesisIn vitro platformMammalian developmentMiceEmbryosNatural embryoGastrulation stageCellsTranscriptional regulationOver-relianceFetusesUtero
2021
Reconstructing aspects of human embryogenesis with pluripotent stem cells
Sozen B, Jorgensen V, Weatherbee B, Chen S, Zhu M, Zernicka-Goetz M. Reconstructing aspects of human embryogenesis with pluripotent stem cells. Nature Communications 2021, 12: 5550. PMID: 34548496, PMCID: PMC8455697, DOI: 10.1038/s41467-021-25853-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingBiomarkersBlastocystCell Culture TechniquesCell LineageEmbryo, MammalianEmbryonic DevelopmentGATA3 Transcription FactorGene ExpressionHumansModels, BiologicalPhospholipase C betaPluripotent Stem CellsSequence Analysis, RNASingle-Cell AnalysisSOXB1 Transcription FactorsSOXF Transcription FactorsConceptsStem cell modelPluripotent stem cellsStem cellsHuman embryogenesisHuman early embryogenesisSingle-cell RNA sequencingEarly embryo developmentHuman early embryo developmentPre-implantation developmentSubsets of cellsStem cell platformsCell identityEarly embryogenesisRNA sequencingCell modelTrophectoderm lineageNatural blastocystsSignaling pathwayClinical importanceCystic structuresExtended cultureEmbryogenesisPre-implantationSignificant divergenceEmbryo developmentMachine learning-assisted high-content analysis of pluripotent stem cell-derived embryos in vitro
Guo J, Wang P, Sozen B, Qiu H, Zhu Y, Zhang X, Ming J, Zernicka-Goetz M, Na J. Machine learning-assisted high-content analysis of pluripotent stem cell-derived embryos in vitro. Stem Cell Reports 2021, 16: 1331-1346. PMID: 33891867, PMCID: PMC8185434, DOI: 10.1016/j.stemcr.2021.03.018.Peer-Reviewed Original Research
2020
Inducible Stem-Cell-Derived Embryos Capture Mouse Morphogenetic Events In Vitro
Amadei G, Lau K, De Jonghe J, Gantner C, Sozen B, Chan C, Zhu M, Kyprianou C, Hollfelder F, Zernicka-Goetz M. Inducible Stem-Cell-Derived Embryos Capture Mouse Morphogenetic Events In Vitro. Developmental Cell 2020, 56: 366-382.e9. PMID: 33378662, PMCID: PMC7883308, DOI: 10.1016/j.devcel.2020.12.004.Peer-Reviewed Original ResearchConceptsEmbryonic stem cellsTrophoblast stem cellsDevelopment of mouse embryosStem cellsXEN cellsTranscription factor GATA4Extra-embryonic mesodermTs cellsExpressed GATA4Mouse embryosAnterior signaling centerAnterior-posterior patterningDevelopmental potentialExtra-embryonic endodermDefinitive endodermMouse gastrulaGATA4Morphogenetic eventsSignaling centersMorphogenic eventsEndodermal fateEmbryosCellsGastrulationEmbryo-like structuresThe dynamics of morphogenesis in stem cell-based embryology: Novel insights for symmetry breaking
Sozen B, Cornwall-Scoones J, Zernicka-Goetz M. The dynamics of morphogenesis in stem cell-based embryology: Novel insights for symmetry breaking. Developmental Biology 2020, 474: 82-90. PMID: 33333067, PMCID: PMC8259461, DOI: 10.1016/j.ydbio.2020.12.005.Peer-Reviewed Original ResearchConceptsSignaling gradientsMorphogen signaling gradientsAnteroposterior axis specificationMammalian embryosBody planAxis specificationSymmetry breakingModel of embryogenesisEmbryonic symmetryEmbryonic cellsPatterns in vivoMolecular processesAdult organismBiochemical mechanismsDynamics of morphogenesisEmbryogenesisIn vitro modelEmbryosModel systemIn vitroCritical processCellsMorphogenMorphogenesisStem cellsBMP signalling is required for extra-embryonic ectoderm development during pre-to-post-implantation transition of the mouse embryo
Sozen B, Demir N, Zernicka-Goetz M. BMP signalling is required for extra-embryonic ectoderm development during pre-to-post-implantation transition of the mouse embryo. Developmental Biology 2020, 470: 84-94. PMID: 33217407, PMCID: PMC8219371, DOI: 10.1016/j.ydbio.2020.11.005.Peer-Reviewed Original ResearchConceptsBMP signalingEctoderm developmentNon-canonical mechanismMouse embryosMechanism of BMPMutant embryosGenetic studiesEarly embryogenesisSignaling pathwayPost-implantation developmentBMP activityTissue organisationStem cell populationStage in vitroSpatiotemporal controlUterine tissueEmbryosCell populationsBMPStem cellsSignalImplantationPost-implantationMiceMorphogenesis
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 differentiationLineagesCells
2018
Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures
Sozen B, Amadei G, Cox A, Wang R, Na E, Czukiewska S, Chappell L, Voet T, Michel G, Jing N, Glover D, Zernicka-Goetz M. Self-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures. Nature Cell Biology 2018, 20: 979-989. PMID: 30038254, DOI: 10.1038/s41556-018-0147-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CommunicationCell DifferentiationCell LineCell LineageCell MovementCoculture TechniquesEmbryo, MammalianEndodermEpithelial-Mesenchymal TransitionGastrulationGene Expression Regulation, DevelopmentalGestational AgeMiceMouse Embryonic Stem CellsPhenotypeTranscriptomeTrophoblastsConceptsStem cell typesEpithelial-mesenchymal transitionStem cellsExtra-embryonic compartmentCell typesTrophoblast stem cellsEndoderm stem cellsEmbryonic stem cellsMammalian embryosSpatial transcriptomic analysisTrophoblastGene expression patternsGerm lineMiceGastrulating embryosEmbryo-like structuresIn 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 conditions
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
2013
Telomere length and telomerase activity during oocyte maturation and early embryo development in mammalian species
Ozturk S, Sozen B, Demir N. Telomere length and telomerase activity during oocyte maturation and early embryo development in mammalian species. Molecular Human Reproduction 2013, 20: 15-30. PMID: 23928157, DOI: 10.1093/molehr/gat055.Peer-Reviewed Original ResearchConceptsGranulosa cellsTelomerase activityProliferative granulosa cellsEarly embryosEarly embryo developmentTelomere lengthProliferative somatic cellsMammalian speciesEffects of oxidative stressOocyte maturationCancer cellsNon-dividing cellsStem cellsAdverse effects of oxidative stressShortened telomeresSomatic cellsOocytesEmbryo developmentAdverse effectsGranulosaGenotoxic agentsOxidative stressGermline cellsComprehensive review articleLength of telomeres