2024
Selective utilization of glucose metabolism guides mammalian gastrulation
Cao D, Bergmann J, Zhong L, Hemalatha A, Dingare C, Jensen T, Cox A, Greco V, Steventon B, Sozen B. Selective utilization of glucose metabolism guides mammalian gastrulation. Nature 2024, 634: 919-928. PMID: 39415005, PMCID: PMC11499262, DOI: 10.1038/s41586-024-08044-1.Peer-Reviewed Original ResearchConceptsCellular metabolismMammalian gastrulationHexosamine biosynthetic pathwayTranscription factor networksCellular signaling pathwaysSignaling morphogensGlucose metabolismCellular programmeBiosynthetic pathwayFate acquisitionCell fateHousekeeping natureGenetic mechanismsMesoderm migrationFactor networksERK activationExpression patternsSignaling pathwayDevelopmental processesStem cell modelCell typesSpecialized functionsDevelopmental contextMammalian embryosMouse embryos
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 domainSelf-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
Human embryo polarization requires PLC signaling to mediate trophectoderm specification
Zhu M, Shahbazi M, Martin A, Zhang C, Sozen B, Borsos M, Mandelbaum RS, Paulson RJ, Mole MA, Esbert M, Titus S, Scott RT, Campbell A, Fishel S, Gradinaru V, Zhao H, Wu K, Chen ZJ, Seli E, de los Santos MJ, Goetz M. Human embryo polarization requires PLC signaling to mediate trophectoderm specification. ELife 2021, 10: e65068. PMID: 34569938, PMCID: PMC8514238, DOI: 10.7554/elife.65068.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdultBody PatterningCell DifferentiationCell LineageCell PolarityEmbryo Culture TechniquesEmbryo, MammalianFemaleGATA3 Transcription FactorGene Expression Regulation, DevelopmentalGene Expression Regulation, EnzymologicHumansPhosphoinositide Phospholipase CPhospholipase C betaPregnancySignal TransductionTime FactorsYoung AdultConceptsApical domain formationInner cell massEmbryo polarizationPhospholipase CFirst lineage segregationApico-basal polarizationEight-cell stageLineage segregationMammalian developmentTrophectoderm specificationTE fateApical enrichmentApical accumulationDistinct lineagesApical domainApolar cellsPar complexPolarized cellsRNA interferenceMolecular mechanismsF-actinHuman embryosCell stageEmbryosDomain formationReconstructing 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 development
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 structuresBMP 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 structures
2015
The p38 MAPK signalling pathway is required for glucose metabolism, lineage specification and embryo survival during mouse preimplantation development
Sozen B, Ozturk S, Yaba A, Demir N. The p38 MAPK signalling pathway is required for glucose metabolism, lineage specification and embryo survival during mouse preimplantation development. Cells And Development 2015, 138: 375-398. PMID: 26025760, DOI: 10.1016/j.mod.2015.05.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBlastocystBlastocyst Inner Cell MassCell DeathCell LineageEmbryonic DevelopmentFemaleGene Expression Regulation, DevelopmentalGlucoseGlucose Transporter Type 1Glucose Transporter Type 4ImidazolesMaleMAP Kinase Signaling SystemMiceMice, Inbred BALB CModels, BiologicalPregnancyProtein Kinase InhibitorsPyridinesRNA, MessengerConceptsPreimplantation developmentP38 mitogen-activated protein kinaseMitogen-activated protein kinaseLate preimplantation stagePreimplantation embryo developmentMouse preimplantation developmentExpression levelsEmbryo developmentEffect of p38 MAPK inhibitionExpression levels of NANOGEarly embryo developmentP38 MAPK inhibitionPresence of SB203580P38 MAPK signaling pathwayLevel of transcriptionIncreased cell deathSignal transduction pathwaysBlastocyst stageExpression levels of transcriptsLevels of NanogP38 MAPK pathwayPreimplantation stagesLevels of GLUT1Expression levels of Glut1MAPK signaling pathway
2014
Cell fate regulation during preimplantation development: A view of adhesion-linked molecular interactions
Sozen B, Can A, Demir N. Cell fate regulation during preimplantation development: A view of adhesion-linked molecular interactions. Developmental Biology 2014, 395: 73-83. PMID: 25176042, DOI: 10.1016/j.ydbio.2014.08.028.Peer-Reviewed Original ResearchConceptsCell fate regulationEarly mammalian embryoFate regulationCell fate specificationMammalian embryosJunctional complexesEvaluate transcriptional differencesTranscriptional networksFate specificationCell polarityIntercellular junctional complexesPreimplantation developmentCellular diversificationTranscriptional differencesDiversification processEmbryonic lineagesEarly embryosCell adhesionDevelopmental processesEarly morphogenesisLineage commitmentIdentical cellsCell positionMolecular interactionsCells