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 ResearchMeSH KeywordsAnimalsBioengineeringEmbryo, MammalianEmbryonic DevelopmentMammalsReproductionStem CellsSelf-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 ResearchMeSH KeywordsAnimalsEmbryo, MammalianEmbryonic DevelopmentGastrulationHumansMammalsMiceOrganoidsPluripotent Stem CellsConceptsEmbryo 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 development
2020
The 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 ResearchMeSH KeywordsAnimalsBody PatterningEmbryo, MammalianEmbryonic DevelopmentHumansMiceMorphogenesisSignal TransductionStem CellsConceptsSignaling 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
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 ResearchMeSH KeywordsAnimalsEmbryonic DevelopmentMiceModels, BiologicalMouse Embryonic Stem CellsOrgan Culture TechniquesTrophoblastsConceptsTrophoblast 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
Differential 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
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
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 mechanismsEmbryos
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