The pluripotency transcription factor Nanog represses glutathione reductase gene expression in mouse embryonic stem cells

Objective: Redox homeostasis maintenance is essential to bring about cellular functions. Particularly, embryonic stem cells (ESCs) have high fidelity mechanisms for DNA repair, high activity of different antioxidant enzymes and low levels of oxidative stress. Although the expression and activity of...

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Detalles Bibliográficos
Autores: Solari, Claudia María, Petrone Parcero, María Victoria, Toro, Ayelen Rayen, Vazquez Echegaray, Camila, Cosentino, María Soledad, Waisman, Ariel, Francia, Marcos Gabriel, Barañao, Jose Lino Salvador, Miriuka, Santiago Gabriel, Guberman, Alejandra Sonia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/119834
Acceso en línea:http://hdl.handle.net/11336/119834
Access Level:acceso abierto
Palabra clave:DIFFERENTIATION
EMBRYONIC STEM CELLS
GENE EXPRESSION
GLUTATHIONE REDUCTASE
NANOG
REDOX HOMEOSTASIS
TRANSCRIPTIONAL REGULATION
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descripción
Sumario:Objective: Redox homeostasis maintenance is essential to bring about cellular functions. Particularly, embryonic stem cells (ESCs) have high fidelity mechanisms for DNA repair, high activity of different antioxidant enzymes and low levels of oxidative stress. Although the expression and activity of antioxidant enzymes are reduced throughout the differentiation, the knowledge about the transcriptional regulation of genes involved in defense against oxidative stress is yet restricted. Since glutathione is a central component of a complex system involved in preserving cellular redox status, we aimed to study whether the expression of the glutathione reductase (Gsr) gene, which encodes an essential enzyme for cellular redox homeostasis, is modulated by the transcription factors critical for self-renewal and pluripotency of ESCs. Results: We found that Gsr gene is expressed in ESCs during the pluripotent state and it was upregulated when these cells were induced to differentiate, concomitantly with Nanog decreased expression. Moreover, we found an increase in Gsr mRNA levels when Nanog was downregulated by a specific shRNA targeting this transcription factor in ESCs. Our results suggest that Nanog represses Gsr gene expression in ESCs, evidencing a role of this crucial pluripotency transcription factor in preservation of redox homeostasis in stem cells.