2023
Self-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 formationUnfolded 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
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
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