GSE271652
GSE GEOAutism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes [ATAC-seq]
Organism:
Mus musculus
Platform:
GPL24247
Samples:
9
Experiment Types:
Genome binding/occupancy profiling by high throughput sequencing
Submitted:
Jul 07 2024
Last Updated:
Oct 08 2024
Status:
Public on Jul 09 2024
Contact:
Platon,,Megagiannis (McGill University)
Relations
BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1132699
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.
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
Analysis (5 steps)
View Data Processing
Processing steps for GSE271652
- Reads were downsampled to an equivalent number of reads per sample using seqtk sample (version 1.2)
- Adaptors were trimmed with trimmomatic (version 0.39) [1] with the options ILLUMINACLIP:Trimmomatic-0.39/adapters/NexteraPE-PE.fa:2:30:10 LEADING:3 TRAILING:3 SLIDINGWINDOW:4:25 MINLEN:24
- Reads were then aligned to the mouse genome (mm10) with bowtie2 (version 2.4.4) using default parameters
- Duplicates were removed with picard through gatk MarkDuplicates (version 4.2.5.0)
- Peak detection was performed using macs2 callpeak (version 2.2.7.1) with the parameters â-g mm --qvalue 0.05 --shift 100 --extsize 200 --format BAMPE --keep-dup=all --cutoff-analysis âbdgââ.
Supplementary Files (1)
GSE271652_RAW.tar
Download
GEO Samples (9)
Dataset Citations (1)
Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes.
PMID 39154337
· 2024
· Cell reports
Platon Megagiannis, Yuan Mei, Rachel E Yan, Lin Yuan, Jonathan J Wilde, Hailey Eckersberg, Rahul Suresh, Xinzhu Tan, Hong Chen, W Todd Farmer, Kuwook Cha, Phuong Uyen Le, Helene Catoire, Daniel Rochefort, Tony Kwan, Brian A Yee, Patrick Dion, Arjun Krishnaswamy, Jean-Francois Cloutier, Stefano Stifani, Kevin Petrecca, Gene W Yeo, Keith K Murai, Guoping Feng, Guy A Rouleau, Trey Ideker, Neville E Sanjana, Yang Zhou
SRA Experiments (9) and Runs (9)
Total: 30699 MBGSM8381216: Cortex, Saline, 3days, control A1; Mus musculus; ATAC-seq
Sample: SRS21916317
BioProject: PRJNA1132699
BioSample: SAMN42353249
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: astrocyte enriched samples
genotype: Control Saline 1
treatment: Lipopolysaccharide
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727704 | 47204654 | 9535340108 | 2958.66 | WT1_A01_ZHO2243A1-1_S1_L002_R1_001.fastq.gz, WT1_A01_ZHO2243A1-1_S1_L… | SRA |
GSM8381217: Cortex, Saline, 3days, control A2; Mus musculus; ATAC-seq
Sample: SRS21916318
BioProject: PRJNA1132699
BioSample: SAMN42353248
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: astrocyte enriched samples
genotype: Control Saline 2
treatment: Lipopolysaccharide
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727703 | 53999830 | 10907965660 | 3385.67 | WT2_A02_ZHO2243A2-1_S2_L002_R1_001.fastq.gz, WT2_A02_ZHO2243A2-1_S2_L… | SRA |
GSM8381218: Cortex, Saline, 3days, control A3; Mus musculus; ATAC-seq
Sample: SRS21916319
BioProject: PRJNA1132699
BioSample: SAMN42353247
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: astrocyte enriched samples
genotype: Control Saline 3
treatment: Lipopolysaccharide
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727700 | 52188698 | 10542116996 | 3292.67 | WT3_A03_ZHO2243A3-1_S3_L002_R1_001.fastq.gz, WT3_A03_ZHO2243A3-1_S3_L… | SRA |
GSM8381219: Cortex, LPS, 3days, control B1; Mus musculus; ATAC-seq
Sample: SRS21916320
BioProject: PRJNA1132699
BioSample: SAMN42353246
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: astrocyte enriched samples
genotype: Control LPS 1
treatment: Lipopolysaccharide
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727699 | 51508161 | 10404648522 | 3235.23 | WTLPS1_B01_ZHO2243A4-1_S4_L002_R1_001.fastq.gz, WTLPS1_B01_ZHO2243A4-… | SRA |
GSM8381220: Cortex, LPS, 3days, control B2; Mus musculus; ATAC-seq
Sample: SRS21916321
BioProject: PRJNA1132699
BioSample: SAMN42353245
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: astrocyte enriched samples
genotype: Control LPS 2
treatment: Lipopolysaccharide
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727701 | 58481422 | 11813247244 | 3660.88 | WTLPS2_B02_ZHO2243A5-1_S5_L002_R1_001.fastq.gz, WTLPS2_B02_ZHO2243A5-… | SRA |
GSM8381221: Cortex, LPS, 3days, control B3; Mus musculus; ATAC-seq
Sample: SRS21916322
BioProject: PRJNA1132699
BioSample: SAMN42353244
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: astrocyte enriched samples
genotype: Control LPS 3
treatment: Lipopolysaccharide
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727698 | 57678983 | 11651154566 | 3591.64 | WTLPS3_B03_ZHO2243A6-1_S6_L002_R1_001.fastq.gz, WTLPS3_B03_ZHO2243A6-… | SRA |
GSM8381222: Cortex, LPS, 3days, astrocyte cKO C1; Mus musculus; ATAC-seq
Sample: SRS21916323
BioProject: PRJNA1132699
BioSample: SAMN42353243
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: astrocyte enriched samples
genotype: Astrocyte cKO LPS 1
treatment: Lipopolysaccharide
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727702 | 50000750 | 10100151500 | 3499.09 | cKOLPS1_C01_ZHO2243A7-1_S7_L002_R1_001.fastq.gz, cKOLPS1_C01_ZHO2243A… | SRA |
GSM8381223: Cortex, LPS, 3days, astrocyte cKO C2; Mus musculus; ATAC-seq
Sample: SRS21916324
BioProject: PRJNA1132699
BioSample: SAMN42353242
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: astrocyte enriched samples
genotype: Astrocyte cKO LPS 2
treatment: Lipopolysaccharide
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727697 | 56560604 | 11425242008 | 3575.61 | cKOLPS2_C02_ZHO2243A8-1_S8_L002_R1_001.fastq.gz, cKOLPS2_C02_ZHO2243A… | SRA |
GSM8381224: Cortex, LPS, 3days, astrocyte cKO C3; Mus musculus; ATAC-seq
Sample: SRS21916325
BioProject: PRJNA1132699
BioSample: SAMN42353241
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: astrocyte enriched samples
genotype: Astrocyte cKO LPS 3
treatment: Lipopolysaccharide
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727696 | 55432837 | 11197433074 | 3499.93 | cKOLPS3_C03_ZHO2243A9-1_S9_L002_R1_001.fastq.gz, cKOLPS3_C03_ZHO2243A… | SRA |
Linked Publications (2)
Data Files (9)
| Accession | File Name | Stored Type | Output Type | Mapping Assembly | Size | Download | |
|---|---|---|---|---|---|---|---|
| — | cKOLPS1_C01_ZHO2243A7-1_S7_L002_R1_001.fastq.gz | ATAC-seq | 3.4 GB | link | |||
| — | cKOLPS2_C02_ZHO2243A8-1_S8_L002_R1_001.fastq.gz | ATAC-seq | 3.5 GB | link | |||
| — | cKOLPS3_C03_ZHO2243A9-1_S9_L002_R1_001.fastq.gz | ATAC-seq | 3.4 GB | link | |||
| — | WT1_A01_ZHO2243A1-1_S1_L002_R1_001.fastq.gz | ATAC-seq | 2.9 GB | link | |||
| — | WT2_A02_ZHO2243A2-1_S2_L002_R1_001.fastq.gz | ATAC-seq | 3.3 GB | link | |||
| — | WT3_A03_ZHO2243A3-1_S3_L002_R1_001.fastq.gz | ATAC-seq | 3.2 GB | link | |||
| — | WTLPS1_B01_ZHO2243A4-1_S4_L002_R1_001.fastq.gz | ATAC-seq | 3.2 GB | link | |||
| — | WTLPS2_B02_ZHO2243A5-1_S5_L002_R1_001.fastq.gz | ATAC-seq | 3.6 GB | link | |||
| — | WTLPS3_B03_ZHO2243A6-1_S6_L002_R1_001.fastq.gz | ATAC-seq | 3.5 GB | link |