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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
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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.
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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
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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 |
Citation missing |
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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
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Organization name |
Karolinska Institutet
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Department |
Physiology and Pharmacology
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Lab |
MCEP
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Street address |
Solnavägen 9
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City |
Solna |
ZIP/Postal code |
17165 |
Country |
Sweden |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (15)
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GSM7916071 |
Astrocytes, GFP adenovirus infected, rep1 |
GSM7916072 |
Astrocytes, GFP adenovirus infected, rep2 |
GSM7916073 |
Astrocytes, GFP adenovirus infected, rep3 |
GSM7916074 |
Astrocytes, PGC-1a1 adenovirus infected, rep1 |
GSM7916075 |
Astrocytes, PGC-1a1 adenovirus infected, rep2 |
GSM7916076 |
Astrocytes, PGC-1a1 adenovirus infected, rep3 |
GSM7916077 |
Astrocytes, PGC-1a2 adenovirus infected, rep1 |
GSM7916078 |
Astrocytes, PGC-1a2 adenovirus infected, rep2 |
GSM7916079 |
Astrocytes, PGC-1a2 adenovirus infected, rep3 |
GSM7916080 |
Astrocytes, PGC-1a3 adenovirus infected, rep1 |
GSM7916081 |
Astrocytes, PGC-1a3 adenovirus infected, rep2 |
GSM7916082 |
Astrocytes, PGC-1a3 adenovirus infected, rep3 |
GSM7916083 |
Astrocytes, PGC-1a4 adenovirus infected, rep1 |
GSM7916084 |
Astrocytes, PGC-1a4 adenovirus infected, rep2 |
GSM7916085 |
Astrocytes, PGC-1a4 adenovirus infected, rep3 |
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Relations |
BioProject |
PRJNA1044140 |
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 |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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