2024
Mannose 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
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 domainWhat approaches are needed to understand human development and disease?
Sozen B, Flavell R, Lamming D, Silver D, Parrinello S, Abate-Shen C, Michor F, Sankaran V. What approaches are needed to understand human development and disease? Developmental Cell 2023, 58: 2822-2825. PMID: 38113848, DOI: 10.1016/j.devcel.2023.11.026.Peer-Reviewed Original ResearchShifting 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 typesA Spatiotemporal Compartmentalization of Glucose Metabolism Guides Mammalian Gastrulation Progression.
Cao D, Zhong L, Hemalatha A, Bergmann J, Cox AL, Greco V, Sozen B. A Spatiotemporal Compartmentalization of Glucose Metabolism Guides Mammalian Gastrulation Progression. BioRxiv 2023 PMID: 37333168, DOI: 10.1101/2023.06.06.543780.Peer-Reviewed Original Research In Press
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
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 developmentUnfolded protein response triggers differential apoptotic mechanisms in ovaries and early embryos exposed to maternal type 1 diabetes
Okan A, Demir N, Sozen B. Unfolded protein response triggers differential apoptotic mechanisms in ovaries and early embryos exposed to maternal type 1 diabetes. Scientific Reports 2021, 11: 12759. PMID: 34140543, PMCID: PMC8211688, DOI: 10.1038/s41598-021-92093-3.Peer-Reviewed Original ResearchConceptsUnfolded protein responseProtein responseER stressDiabetes mellitusFemale mammalian reproductive systemEndoplasmic reticulum (ER)-stressMaternal type 1 diabetesEmbryonic developmentActivation of ER stressMammalian ovarian functionType 1 DMIn vivo mouse modelInduced developmental programAdult ovarian tissueEffect of DMMammalian reproductive systemEarly embryonic developmentEarly embryo developmentPre-implantation embryosType 1 diabetesApoptotic cascadeDiabetic ovariesMaternal DMActivated CHOPCaspase 12Machine 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-implantationMiceMorphogenesisAre There Any Sex-Depended Differences in Water Transporting Proteins of Choroid Plexus in Mice?
Sözen B, Aytaç G, Demir N, Süzen B, Tanrıöver G. Are There Any Sex-Depended Differences in Water Transporting Proteins of Choroid Plexus in Mice? Journal Of Basic And Clinical Health Sciences 2020 DOI: 10.30621/jbachs.2020.1010.Peer-Reviewed Original Research
2019
Correction to: FoxO transcription factors regulate mouse preimplantation embryo development
Kuscu N, Gungor-Ordueri N, Sozen B, Adiguzel D, Celik-Ozenci C. Correction to: FoxO transcription factors regulate mouse preimplantation embryo development. Journal Of Assisted Reproduction And Genetics 2019, 36: 2605-2605. PMID: 31802347, PMCID: PMC6911125, DOI: 10.1007/s10815-019-01645-0.Peer-Reviewed Original ResearchSelf-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 differentiationLineagesCellsDehydroepiandrosterone supplementation attenuates ovarian ageing in a galactose-induced primary ovarian insufficiency rat model
Sozen B, Ozekinci M, Erman M, Gunduz T, Demir N, Akouri R. Dehydroepiandrosterone supplementation attenuates ovarian ageing in a galactose-induced primary ovarian insufficiency rat model. Journal Of Assisted Reproduction And Genetics 2019, 36: 2181-2189. PMID: 31422495, PMCID: PMC6823469, DOI: 10.1007/s10815-019-01560-4.Peer-Reviewed Original ResearchConceptsPrimary ovarian insufficiencyDehydroepiandrosterone treatmentOvarian agingDecreased follicle numberReduced follicle poolPrimordial follicle recruitmentGalactose-containing dietOvarian follicle countsEffect of dehydroepiandrosteroneExpression of Ki67 proteinBody weightApoptosis marker expressionExpression of cleaved-caspase-3MethodsPregnant ratsOffspring ovariesFollicle poolOvarian insufficiencyFollicle countCell death assessmentFollicle recruitmentOvarian tissueIncreased atresiaKi67 proteinRat modelGroup 2FoxO 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 embryosSelf-Assembly of Embryonic and Two Extraembryonic 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 Extraembryonic Stem Cell Types Into Gastrulating Embryo-like Structures. Obstetrical & Gynecological Survey 2019, 74: 30-31. DOI: 10.1097/01.ogx.0000553115.73937.07.Peer-Reviewed Original Research