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
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 12
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 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 cells
2019
Dehydroepiandrosterone 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 embryos
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 developmentTwist1The poly(A)-binding protein genes, EPAB, PABPC1, and PABPC3 are differentially expressed in infertile men with non-obstructive azoospermia
Ozturk S, Sozen B, Uysal F, Bassorgun I, Usta M, Akkoyunlu G, Demir N. The poly(A)-binding protein genes, EPAB, PABPC1, and PABPC3 are differentially expressed in infertile men with non-obstructive azoospermia. Journal Of Assisted Reproduction And Genetics 2016, 33: 335-348. PMID: 26843391, PMCID: PMC4785164, DOI: 10.1007/s10815-016-0654-z.Peer-Reviewed Original ResearchConceptsPoly(A)-binding proteinNon-obstructive azoospermiaPoly(A)-binding protein geneSertoli cell-only syndromeTesticular biopsy samplesRound spermatidsPABP expressionExpression levelsIsolated spermatocytesTranslational controlProtein geneInfertile menPABPC1Male infertilitySpermatocytesPABPC3MRNA expressionArrest groupEPABSco groupBiopsy samplesMolecular backgroundProteinAzoospermiaEvaluate expression levels
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 stageCell 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
2012
Ultrastructural analysis of vascular features in cerebral cavernous malformations
Tanriover G, Sozen B, Seker A, Kilic T, Gunel M, Demir N. Ultrastructural analysis of vascular features in cerebral cavernous malformations. Clinical Neurology And Neurosurgery 2012, 115: 438-444. PMID: 22776801, DOI: 10.1016/j.clineuro.2012.06.023.Peer-Reviewed Original ResearchMeSH KeywordsApoptosis Regulatory ProteinsBlood VesselsBrainCarrier ProteinsCerebrovascular CirculationChromosome MappingEndothelium, VascularGene Expression RegulationHumansImmunohistochemistryIntracranial Arteriovenous MalformationsKRIT1 ProteinMembrane ProteinsMicroscopy, Electron, ScanningMicroscopy, Electron, TransmissionMicrotubule-Associated ProteinsNeurogliaPericytesPlatelet Endothelial Cell Adhesion Molecule-1Proto-Oncogene ProteinsStromal CellsConceptsCerebral cavernous malformationsVascular malformationsCavernous malformationsUltrastructural featuresBasal laminaIntact basal laminaHuman CCM lesionsConventional indicationsClinical behaviorThin vessel wallWeak immunostainingCCM lesionsVascular endotheliumPathogenic mechanismsLuminal endotheliumVascular featuresMalformationsEndothelial cellsEndotheliumVessel wallLesionsUltrastructural analysisIntercellular junctionsFirst studyRupture
2011
CCM2 expression during prenatal development and adult human neocortex
Tanriover G, Sozen B, Gunel M, Demir N. CCM2 expression during prenatal development and adult human neocortex. International Journal Of Developmental Neuroscience 2011, 29: 509-514. PMID: 21569831, DOI: 10.1016/j.ijdevneu.2011.04.006.Peer-Reviewed Original ResearchConceptsAdult human neocortexCerebral cavernous malformationsHuman neocortexNeuroglial precursor cellsPrenatal developmentMeans of immunohistochemistryCentral nervous systemWestern blot analysisHuman brain developmentVascular malformationsAdult neocortexGlial cellsCavernous malformationsCCM lesionsVascular endotheliumNervous systemVascular channelsBlood vessel formationArterial endotheliumBrain developmentNeocortexExpression patternsEndotheliumPrecursor cellsCCM loci