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dc.contributor.author
Sanhueza Salas, L. Francisco
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García Venzor, Alfredo
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Beltramone, Natalia
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Capurro, Claudia Graciela
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Toiber, Debra
dc.contributor.author
Silberman, Dafne Magalí
dc.date.available
2022-09-13T14:12:52Z
dc.date.issued
2021-11
dc.identifier.citation
Sanhueza Salas, L. Francisco; García Venzor, Alfredo; Beltramone, Natalia; Capurro, Claudia Graciela; Toiber, Debra; et al.; Metabolic Imbalance Effect on Retinal Müller Glial Cells Reprogramming Capacity: Involvement of Histone Deacetylase SIRT6; Frontiers Media; Frontiers in Genetics; 12; 11-2021; 1-12
dc.identifier.issn
1664-8021
dc.identifier.uri
http://hdl.handle.net/11336/168526
dc.description.abstract
Retinal Müller glial cells (MGs) are among the first to demonstrate metabolic changes during retinal disease and are a potential source of regenerative cells. In response to a harmful stimulus, they can dedifferentiate acquiring neural stem cells properties, proliferate and migrate to the damaged retinal layer and differentiate into lost neurons. However, it is not yet known how this reprogramming process is regulated in mammals. Since glucose and oxygen are important regulatory elements that may help directing stem cell fate, we aimed to study the effect of glucose variations and oxidative stress in Müller cells reprogramming capacity and analyze the participation the histone deacetylase SIRT6, as an epigenetic modulator of this process. We found that the combination of high glucose and oxidative stress induced a decrease in the levels of the marker glutamine synthetase, and an increase in the migration capacity of the cells suggesting that these experimental conditions could induce some degree of dedifferentiation and favor the migration ability. High glucose induced an increase in the levels of the pluripotent factor SOX9 and a decrease in SIRT6 levels accompanied by the increase in the acetylation levels of H3K9. Inhibiting SIRT6 expression by siRNA rendered an increase in SOX9 levels. We also determined SOX9 levels in retinas from mice with a conditional deletion of SIRT6 in the CNS. To further understand the mechanisms that regulate MGs response under metabolic impaired conditions, we evaluated the gene expression profile and performed Gene Ontology enrichment analysis of Müller cells from a murine model of Diabetes. We found several differentially expressed genes and observed that the transcriptomic change involved the enrichment of genes associated with glucose metabolism, cell migration, development and pluripotency. We found that many functional categories affected in cells of diabetic animals were directly related to SIRT6 function. Transcription factors enrichment analysis allowed us to predict several factors, including SOX9, that may be involved in the modulation of the differential expression program observed in diabetic MGs. Our results underline the heterogeneity of Müller cells response and the challenge that the study of metabolic impairment in vivo represents.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Frontiers Media
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
METABOLISM
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MÜLLER CELLS
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REPROGRAMMING
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RETINA
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SIRT6
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Metabolic Imbalance Effect on Retinal Müller Glial Cells Reprogramming Capacity: Involvement of Histone Deacetylase SIRT6
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-09-07T18:49:09Z
dc.journal.volume
12
dc.journal.pagination
1-12
dc.journal.pais
Suiza
dc.journal.ciudad
Lausanne
dc.description.fil
Fil: Sanhueza Salas, L. Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
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Fil: García Venzor, Alfredo. Ben Gurion University of the Negev; Israel
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Fil: Beltramone, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
dc.description.fil
Fil: Capurro, Claudia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
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Fil: Toiber, Debra. Ben Gurion University of the Negev; Israel
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Fil: Silberman, Dafne Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
dc.journal.title
Frontiers in Genetics
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3389/fgene.2021.769723
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fgene.2021.769723/full
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