title: Manganese Superoxide Dismutase Gene Expression Is Induced by Nanog and Oct4, Essential Pluripotent Stem Cells' Transcription Factors.
abstract: Pluripotent stem cells possess complex systems that protect them from oxidative stress and ensure genomic stability, vital for their role in development. Even though it has been reported that antioxidant activity diminishes along stem cell differentiation, little is known about the transcriptional regulation of the involved genes. The reported modulation of some of these genes led us to hypothesize that some of them could be regulated by the transcription factors critical for self-renewal and pluripotency in embryonic stem cells (ESCs) and in induced pluripotent stem cells (iPSCs). In this work, we studied the expression profile of multiple genes involved in antioxidant defense systems in both ESCs and iPSCs. We found that Manganese superoxide dismutase gene (Mn-Sod/Sod2) was repressed during diverse differentiation protocols showing an expression pattern similar to Nanog gene. Moreover, Sod2 promoter activity was induced by Oct4 and Nanog when we performed a transactivation assay using two different reporter constructions. Finally, we studied Sod2 gene regulation by modulating the expression of Oct4 and Nanog in ESCs by shRNAs and found that downregulation of any of them reduced Sod2 expression. Our results indicate that pluripotency transcription factors positively modulate Sod2 gene transcription.
authors.affiliation: Laboratorio de Regulación Génica en Células Madre, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.|Instituto de Química Biológica (IQUIBICEN), UBA-CONICET, Buenos Aires, Argentina.
authors.forename: Claudia
authors.initials: C
authors.lastname: Solari
authors.affiliation: Laboratorio de Regulación Génica en Células Madre, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.|Instituto de Química Biológica (IQUIBICEN), UBA-CONICET, Buenos Aires, Argentina.
authors.forename: Camila
authors.initials: C
authors.lastname: Vázquez Echegaray
authors.affiliation: Laboratorio de Regulación Génica en Células Madre, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.|Instituto de Química Biológica (IQUIBICEN), UBA-CONICET, Buenos Aires, Argentina.
authors.forename: María Soledad
authors.initials: MS
authors.lastname: Cosentino
authors.affiliation: Laboratorio de Regulación Génica en Células Madre, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.|Instituto de Química Biológica (IQUIBICEN), UBA-CONICET, Buenos Aires, Argentina.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Petrone
authors.affiliation: Laboratorio de Regulación Génica en Células Madre, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.|Instituto de Química Biológica (IQUIBICEN), UBA-CONICET, Buenos Aires, Argentina.
authors.forename: Ariel
authors.initials: A
authors.lastname: Waisman
authors.affiliation: Laboratorio de Regulación Génica en Células Madre, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.|Instituto de Química Biológica (IQUIBICEN), UBA-CONICET, Buenos Aires, Argentina.
authors.forename: Carlos
authors.initials: C
authors.lastname: Luzzani
authors.affiliation: Laboratorio de Regulación Génica en Células Madre, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.|Instituto de Química Biológica (IQUIBICEN), UBA-CONICET, Buenos Aires, Argentina.
authors.forename: Marcos
authors.initials: M
authors.lastname: Francia
authors.affiliation: Laboratório de Sinalização Celular, Departamento de Biofísica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.
authors.forename: Emilly
authors.initials: E
authors.lastname: Villodre
authors.affiliation: Laboratório de Sinalização Celular, Departamento de Biofísica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.
authors.forename: Guido
authors.initials: G
authors.lastname: Lenz
authors.affiliation: Laboratorio de Investigación Aplicada a las Neurociencias (LIAN), Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Buenos Aires, Argentina.|Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Santiago
authors.initials: S
authors.lastname: Miriuka
authors.affiliation: Laboratorio de Regulación Génica en Células Madre, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.|Instituto de Química Biológica (IQUIBICEN), UBA-CONICET, Buenos Aires, Argentina.|Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors.forename: Lino
authors.initials: L
authors.lastname: Barañao
authors.affiliation: Laboratorio de Regulación Génica en Células Madre, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.|Instituto de Química Biológica (IQUIBICEN), UBA-CONICET, Buenos Aires, Argentina.|Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.|Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Guberman
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D034741:RNA, Small Interfering; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C475540:Nanog protein, mouse; C494174:Pou5f1 protein, mouse