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 embryosMannose controls mesoderm specification and symmetry breaking in mouse gastruloids
Dingare C, Cao D, Yang J, Sozen B, Steventon B. Mannose controls mesoderm specification and symmetry breaking in mouse gastruloids. Developmental Cell 2024, 59: 1523-1537.e6. PMID: 38636516, DOI: 10.1016/j.devcel.2024.03.031.Peer-Reviewed Original ResearchConceptsMesoderm specificationFeatures of embryonic developmentWnt pathway regulationEarly mesoderm developmentProtein glycosylationPathway regulationProteomic analysisIntracellular recyclingMesoderm developmentEmbryonic developmentGlycolytic intermediatesMannoseGlucose transportCompetitive inhibitorGlycosylationGlucose removal
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
Machine 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 differentiationLineagesCellsFoxO transcription factors 1 regulate mouse preimplantation embryo development
Kuscu N, Gungor-Ordueri N, Sozen B, Adiguzel D, Celik-Ozenci C. FoxO transcription factors 1 regulate mouse preimplantation embryo development. Journal Of Assisted Reproduction And Genetics 2019, 36: 2121-2133. PMID: 31396850, PMCID: PMC6823425, DOI: 10.1007/s10815-019-01555-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBlastocystCell Cycle CheckpointsCell Cycle ProteinsEmbryonic DevelopmentFas Ligand ProteinFemaleForkhead Box Protein O1Forkhead Box Protein O3Forkhead Transcription FactorsGene Expression Regulation, DevelopmentalHumansMiceP21-Activated KinasesPregnancySirtuin 1Tumor Suppressor Protein p53ConceptsPreimplantation embryo developmentFOXO transcription factorsFas ligandTranscription factorsRelated proteinsProteins regulating apoptosisPreimplantation embryosCell cycle related proteinsCleaved caspase 3 proteinsCell cycle arrestDevelopmental competence of embryosEmbryo developmentMouse preimplantation embryo developmentApoptosis-related proteinsMouse embryosCaspase 3 proteinTwo-cell mouse embryosResveratrol treatmentCompetence of embryosHuman preimplantation embryosMouse preimplantation embryosFOXO genesDUTP nick end labeling assayNick end labeling assayKnockdown embryos
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
2016
Expression of aquaporin-7 and aquaporin-9 in tanycyte cells and choroid plexus during mouse estrus cycle
Yaba A, Sozen B, Suzen B, Demir N. Expression of aquaporin-7 and aquaporin-9 in tanycyte cells and choroid plexus during mouse estrus cycle. Morphologie 2016, 101: 39-46. PMID: 27746040, DOI: 10.1016/j.morpho.2016.09.001.Peer-Reviewed Original ResearchConceptsMouse estrus cycleTanycyte cellsAQP-7Family of transmembrane proteinsEpithelial cells of choroid plexusPotential energy substratesExpression of aquaporin 7Oestrous cycleTransmembrane proteinsGlycerol transportRegulate reproductive functionMetestrus stageAquaporin 7Differential staining patternsProestrus stageAQP-9Diestrus stageProteinChoroid plexusEstrus stageHormonal controlMedian eminenceEpithelial cellsAquaporin-9Weak immunoreactivityDifferential expression pattern of Twist1 in mouse preimplantation embryos suggests its multiple roles during early development
Sozen B, Pehlivanoglu S, Demir N. Differential expression pattern of Twist1 in mouse preimplantation embryos suggests its multiple roles during early development. Journal Of Assisted Reproduction And Genetics 2016, 33: 1533-1540. PMID: 27544279, PMCID: PMC5125151, DOI: 10.1007/s10815-016-0794-1.Peer-Reviewed Original ResearchConceptsMouse preimplantation embryosInner cell massDouble immunofluorescence stainingCulture of embryosEarly embryo developmentExpression of Twist1Blastocyst developmentPreimplantation developmentPreimplantation embryosPresence of high glucoseEarly stages of embryosCells of embryosBlastocystImmunofluorescence stainingTwist-related protein 1Stages of embryosRegulation of TwistPurposeThe purposeUniform stainingLineage segregationTwist1 expressionProtein 1Protein levelsEmbryo developmentTwist1
2015
CD90 and CD105 expression in the mouse ovary and testis at different stages of postnatal development
Tepekoy F, Ozturk S, Sozen B, Ozay R, Akkoyunlu G, Demir N. CD90 and CD105 expression in the mouse ovary and testis at different stages of postnatal development. Reproductive Biology 2015, 15: 195-204. PMID: 26679159, DOI: 10.1016/j.repbio.2015.10.004.Peer-Reviewed Original ResearchConceptsExpression of CD90Postnatal developmentGerm cellsPostnatal dayCell typesSomatic cellsGerm cell compartmentMesenchymal stem cell markersStem cell markersStages of gonadal developmentStages of postnatal developmentExpression of CD105Female gonadal cellsMouse gonadsSertoli cellsPostnatal gonadsTesticular expressionMouse ovariesGonadal cellsCD105 expressionCell markersGonadal developmentAdult ovariesImmunohistochemical localizationCD105The 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
Epab and Pabpc1 are differentially expressed in the postnatal mouse ovaries
Ozturk S, Sozen B, Demir N. Epab and Pabpc1 are differentially expressed in the postnatal mouse ovaries. Journal Of Assisted Reproduction And Genetics 2014, 32: 137-146. PMID: 25370180, PMCID: PMC4294878, DOI: 10.1007/s10815-014-0362-5.Peer-Reviewed Original ResearchConceptsPostnatal mouse ovariesCumulus-oocyte complexesMouse ovariesPABPC1 genePrepubertal ovariesGranulosa cellsGerm cellsPrepubertal mouse ovariesEarly preimplantation embryosOvarian follicle countsCytoplasm of oocytesRNA in situ hybridizationReal-time polymerase chain reactionVertebrate germ cellsExpression levelsMII oocytesOocyte complexesPostnatal ovaryCumulus cellsPreimplantation embryosFollicle countPABPC1 expressionQuantitative real-time polymerase chain reactionPolymerase chain reactionFollicular stageUnfolded protein response prevents blastocyst formation during preimplantation embryo development in vitro
Basar M, Bozkurt I, Guzeloglu-Kayisli O, Sozen B, Tekmen I, Schatz F, Arici A, Lockwood CJ, Kayisli UA. Unfolded protein response prevents blastocyst formation during preimplantation embryo development in vitro. Fertility And Sterility 2014, 102: 1777-1784. PMID: 25305729, DOI: 10.1016/j.fertnstert.2014.09.004.Peer-Reviewed Original ResearchConceptsUnfolded protein responseProtein responseBlastocyst formationEmbryo developmentActivation of UPRPreimplantation embryo developmentTM treatmentBlastocyst developmentEffect of tunicamycinEndoplasmic reticulum stressEmbryonic developmentER stressCell embryosNuclear fragmentationMorphological differencesImmunoglobulin proteinBlastocyst stageReticulum stressTunicamycinDevelopment ratePregnant mare serum gonadotropinBlastocyst development rateProtein-1 mRNA expressionNongenomic mechanismsEmbryosCell 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
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