Metabolic Imbalance Effect on Retinal Müller Glial Cells Reprogramming Capacity: Involvement of Histone Deacetylase SIRT6

• DOI: 10.3389/fgene.2021.769723
• Publication Date: 2021-11-04T06:36:06Z
• Authors: L Francisco Sanhu...; Alfredo García-Ve...; Natalia Beltramone; Claudia Capurro; Debra Toiber; Dafne Magalí Silb...
• Keywords: Reprogramming; SIRT6

Retinal Müller glial cells (MGs) are among the first to demonstrate metabolic changes during retinal disease and a potential source of regenerative cells. In response harmful stimulus, they can dedifferentiate acquiring neural stem properties, proliferate migrate damaged layer differentiate into lost neurons. However, it is not yet known how this reprogramming process regulated in mammals. Since glucose oxygen important regulatory elements that may help directing cell fate, we aimed study effect variations oxidative stress capacity analyze participation histone deacetylase SIRT6, as an epigenetic modulator process. We found combination high induced decrease levels marker glutamine synthetase, increase migration suggesting these experimental conditions could induce some degree dedifferentiation favor ability. High pluripotent factor SOX9 SIRT6 accompanied by acetylation H3K9. Inhibiting expression siRNA rendered levels. also determined retinas from mice with conditional deletion CNS. To further understand mechanisms regulate MGs under impaired conditions, evaluated gene profile performed Gene Ontology enrichment analysis murine model Diabetes. several differentially expressed genes observed transcriptomic change involved associated metabolism, migration, development pluripotency. many functional categories affected diabetic animals were directly related function. Transcription factors allowed us predict factors, including SOX9, be modulation differential program MGs. Our results underline heterogeneity challenge impairment vivo represents.