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| Status |
Public on Jul 09, 2024 |
| Title |
Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes [Microglia RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Reactive changes of glial cells during neuroinflammation impact brain disorders and disease progression. Elucidating the mechanisms that control reactive gliosis may help understand brain pathophysiology and improve outcomes. Here, we report that adult ablation of the ASD-associated CHD8 in astrocytes attenuates reactive gliosis via remodeling chromatin accessibility, changing gene expression. Conditional Chd8 deletion in astrocytes, but not microglia, suppresses reactive gliosis by impeding astrocyte proliferation and morphological elaboration. Astrocyte Chd8 ablation alleviates lipopolysaccharide-induced neuroinflammation and septic-associated hypothermia in mice. Astrocytic CHD8 plays an important role in neuroinflammation by altering the chromatin landscape, regulating metabolic and lipid-associated pathways, and astrocyte-microglia crosstalk. Moreover, we show that reactive gliosis can be directly mitigated in vivo using an AAV-mediated Chd8 gene editing strategy. These findings uncover a role of ASD-associated CHD8 in the adult brain, which may warrant future exploration of targeting epigenetic pathways in reactive gliosis and neuroinflammation in injury and neurological diseases.
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| Overall design |
Bulk tissue RNA seq from cortex samples of mice with astrocyte specific Chd8 cKO after LPS or Saline injections, compared to controls. This designed was chosen to probe for transcriptional changes after Chd8 cKO in astrocytes at the baseline and during neuroinflammation
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/39154337/
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| Contributor(s) |
Megagiannis P, Mei Y, Kwan T, Ideker T, Zhou Y |
| Citation(s) |
39154337 |
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| Submission date |
Jul 07, 2024 |
| Last update date |
Oct 08, 2024 |
| Contact name |
Platon Megagiannis |
| E-mail(s) |
platon.megagiannis@mail.mcgill.ca
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| Phone |
4388765272
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| Organization name |
McGill University
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| Department |
Neurology and Neurosurgery
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| Lab |
Yang Zhou lab
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| Street address |
3801 Rue University
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| City |
Montréal |
| State/province |
QC |
| ZIP/Postal code |
H3A 2B4 |
| Country |
Canada |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (9)
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| GSM8381207 |
Microglia-Cortex, Saline, 3days, Control Saline Sample A1 |
| GSM8381208 |
Microglia-Cortex, Saline, 3days, Control Saline Sample A2 |
| GSM8381209 |
Microglia-Cortex, Saline, 3days, Control Saline Sample A3 |
| GSM8381210 |
Microglia-Cortex, Saline, 3days, Control LPS Sample B1 |
| GSM8381211 |
Microglia-Cortex, Saline, 3days, Control LPS Sample B2 |
| GSM8381212 |
Microglia-Cortex, Saline, 3days, Control LPS Sample B3 |
| GSM8381213 |
Microglia-Cortex, Saline, 3days, cKO Saline Sample C1 |
| GSM8381214 |
Microglia-Cortex, Saline, 3days, cKO Saline Sample C2 |
| GSM8381215 |
Microglia-Cortex, Saline, 3days, cKO Saline Sample C3 |
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| Relations |
| BioProject |
PRJNA1132698 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE271651_Microglia_RNAseq_DEGs.xlsx |
8.6 Mb |
(ftp)(http) |
XLSX |
| GSE271651_Normalized_counts_microglia_RNA_seq.xlsx |
2.7 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
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