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Series GSE248504 Query DataSets for GSE248504
Status Public on Nov 27, 2023
Title Sustained PGC-1α2 or PGC-1α3 expression induces astrocyte dysfunction and degeneration.
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) transcriptional coactivators are key regulators of energy metabolism-related genes and are expressed in energy-demanding tissues. There are several PGC-1α variants with different biological functions in different tissues. The brain is one of the tissues where the role of PGC-1α isoforms remains less explored. Here, we used a toxin-based mouse model of Parkinson's disease (PD) and observed that the expression levels of variants PGC-1α2 and PGC-1α3 in the nigrostriatal pathway increases at the onset of dopaminergic cell degeneration. This increase occurs concomitant with an increase in glial fibrillary acidic protein levels. Since PGC-1α coactivators regulate cellular adaptive responses, we hypothesized that they could be involved in the modulation of astrogliosis induced by MPTP. Therefore, we analysed the transcriptome of astrocytes transduced with expression vectors encoding PGC-1α1 to 1α4 by massively parallel sequencing (RNA-seq) and identified the main cellular pathways controlled by these isoforms. Interestingly, in reactive astrocytes the inflammatory and antioxidant responses, adhesion, migration, and viability were altered by PGC-1α2 and PGC-1α3, showing that sustained expression of these isoforms induces astrocyte dysfunction and degeneration. This work highlights PGC-1α isoforms as modulators of astrocyte reactivity and potential therapeutic targets for the treatment of PD and other neurodegenerative disorders.
 
Overall design Comparative gene expression profiling analysis of RNA-seq data from primary mouse astrocytes infected with adenovirus endoding either PGC-1α isoforms or GFP as a control. Experiment contains three replicates for each condition
 
Contributor(s) Nunes MJ, Carvalho AN, Sá-Lemos C, Colaço M, Cervenka I, Ciraci V, Santos SG, Ribeiro MM, Castanheira M, Jannig PR, Gama MJ, Castro-Caldas M, Rodrigues CP, Rodrigues E, Ruas JL
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Submission date Nov 22, 2023
Last update date Nov 27, 2023
Contact name Igor Cervenka
E-mail(s) igor.cervenka@ki.se
Organization name Karolinska Institutet
Department Physiology and Pharmacology
Lab MCEP
Street address Solnavägen 9
City Solna
ZIP/Postal code 17165
Country Sweden
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (15)
GSM7916071 Astrocytes, GFP adenovirus infected, rep1
GSM7916072 Astrocytes, GFP adenovirus infected, rep2
GSM7916073 Astrocytes, GFP adenovirus infected, rep3
Relations
BioProject PRJNA1044140

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE248504_alpha1_vs_gfp_deseq.txt.gz 1.6 Mb (ftp)(http) TXT
GSE248504_alpha2_vs_gfp_deseq.txt.gz 1.5 Mb (ftp)(http) TXT
GSE248504_alpha3_vs_gfp_deseq.txt.gz 1.6 Mb (ftp)(http) TXT
GSE248504_alpha4_vs_gfp_deseq.txt.gz 1.6 Mb (ftp)(http) TXT
GSE248504_pgc1_astro_featureCounts.txt.gz 4.2 Mb (ftp)(http) TXT
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