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GSE271651

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Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes [Microglia RNA-seq]

Organism: Mus musculus
Platform: GPL24247
Samples: 9
Experiment Types:
Expression 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/PRJNA1132698

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 (8 steps)

View Data Processing
Processing steps for GSE271651
  1. Raw reads were trimmed using Trimmomatic.
  2. FastQC (Babraham Bioinformatics) was used before and after trimming to assess quality control.
  3. Reads were aligned to the murine reference genome (mm10) using the STAR aligner tool.
  4. MultiQC (v1.12) was used to assess the quality of alignment.
  5. All aligned samples showed more than 89% uniquely mapped reads.
  6. reads were counted using the FeatureCounts package
  7. Expected gene count quantifications from RSEM analysis were imported into R for differential gene analysis using edgeR (v.3.30.3)
  8. The Goseq tool was used to acquire overrepressented gene categories

Supplementary Files (2)

GSE271651_Microglia_RNAseq_DEGs.xlsx Download
GSE271651_Normalized_counts_microglia_RNA_seq.xlsx Download
GEO Samples (9)
GSM8381207 GSM8381208 GSM8381209 GSM8381210 GSM8381211 GSM8381212 GSM8381213 GSM8381214 GSM8381215

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: 29041 MB
SRX25229838 SRP518355 RNA-Seq PAIRED
GSM8381207: Microglia-Cortex, Saline, 3days, Control Saline Sample A1; Mus musculus; RNA-Seq
Sample: SRS21916300
BioProject: PRJNA1132698
BioSample: SAMN42353240
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: microglia
genotype: Control Saline 1
treatment: Saline
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR29727687 44903228 9070452056 2764.32 WT-1_M_ZHO2261A1-1_S1_L001_R1_001.fastq.gz, WT-1_M_ZHO2261A1-1_S1_L00… SRA
SRX25229839 SRP518355 RNA-Seq PAIRED
GSM8381208: Microglia-Cortex, Saline, 3days, Control Saline Sample A2; Mus musculus; RNA-Seq
Sample: SRS21916302
BioProject: PRJNA1132698
BioSample: SAMN42353239
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: microglia
genotype: Control Saline 2
treatment: Saline
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR29727686 33740173 6815514946 2078.36 WT-2_M_ZHO2261A2-1_S2_L001_R1_001.fastq.gz, WT-2_M_ZHO2261A2-1_S2_L00… SRA
SRX25229840 SRP518355 RNA-Seq PAIRED
GSM8381209: Microglia-Cortex, Saline, 3days, Control Saline Sample A3; Mus musculus; RNA-Seq
Sample: SRS21916301
BioProject: PRJNA1132698
BioSample: SAMN42353238
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: microglia
genotype: Control Saline 3
treatment: Saline
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR29727685 13536234 2734319268 834.12 SRR29727685.lite, SRR29727685, WT-3_M_ZHO2261A3-1_S3_L001_R2_001.fast… SRA
SRX25229841 SRP518355 RNA-Seq PAIRED
GSM8381210: Microglia-Cortex, Saline, 3days, Control LPS Sample B1; Mus musculus; RNA-Seq
Sample: SRS21916303
BioProject: PRJNA1132698
BioSample: SAMN42353237
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: microglia
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
SRR29727684 48556771 9808467742 3000.47 WT-LPS-1_M_ZHO2261A4-1_S4_L001_R1_001.fastq.gz, WT-LPS-1_M_ZHO2261A4-… SRA
SRX25229842 SRP518355 RNA-Seq PAIRED
GSM8381211: Microglia-Cortex, Saline, 3days, Control LPS Sample B2; Mus musculus; RNA-Seq
Sample: SRS21916304
BioProject: PRJNA1132698
BioSample: SAMN42353236
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: microglia
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
SRR29727683 65535902 13238252204 3991.49 WT-LPS-2_M_ZHO2261A5-1_S5_L001_R1_001.fastq.gz, WT-LPS-2_M_ZHO2261A5-… SRA
SRX25229843 SRP518355 RNA-Seq PAIRED
GSM8381212: Microglia-Cortex, Saline, 3days, Control LPS Sample B3; Mus musculus; RNA-Seq
Sample: SRS21916305
BioProject: PRJNA1132698
BioSample: SAMN42353235
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: microglia
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
SRR29727682 52712338 10647892276 3226.44 WT-LPS-3_M_ZHO2261A6-1_S6_L001_R1_001.fastq.gz, WT-LPS-3_M_ZHO2261A6-… SRA
SRX25229844 SRP518355 RNA-Seq PAIRED
GSM8381213: Microglia-Cortex, Saline, 3days, cKO Saline Sample C1; Mus musculus; RNA-Seq
Sample: SRS21916306
BioProject: PRJNA1132698
BioSample: SAMN42353234
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: microglia
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
SRR29727681 43330935 8752848870 2650.74 cKO-LPS-1_M_ZHO2261A7-1_S7_L001_R1_001.fastq.gz, cKO-LPS-1_M_ZHO2261A… SRA
SRX25229845 SRP518355 RNA-Seq PAIRED
GSM8381214: Microglia-Cortex, Saline, 3days, cKO Saline Sample C2; Mus musculus; RNA-Seq
Sample: SRS21916307
BioProject: PRJNA1132698
BioSample: SAMN42353233
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: microglia
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
SRR29727680 62783584 12682283968 3829.94 cKO-LPS-2_M_ZHO2261A8-1_S8_L001_R1_001.fastq.gz, cKO-LPS-2_M_ZHO2261A… SRA
SRX25229846 SRP518355 RNA-Seq PAIRED
GSM8381215: Microglia-Cortex, Saline, 3days, cKO Saline Sample C3; Mus musculus; RNA-Seq
Sample: SRS21916308
BioProject: PRJNA1132698
BioSample: SAMN42353232
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: microglia
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
SRR29727679 109468004 22112536808 6665.39 cKO-LPS-3_M_ZHO2261A9-1_S9_L001_R1_001.fastq.gz, cKO-LPS-3_M_ZHO2261A… SRA

Linked Publications (2)

Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes.
Cell reports · 2024
Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes.
Cell reports · 2024

Data Files (10)

Accession File Name Stored Type Output Type Mapping Assembly Size Download
— cKO-LPS-1_M_ZHO2261A7-1_S7_L001_R1_001.fastq.gz RNA-Seq 2.6 GB link
— cKO-LPS-2_M_ZHO2261A8-1_S8_L001_R1_001.fastq.gz RNA-Seq 3.7 GB link
— cKO-LPS-3_M_ZHO2261A9-1_S9_L001_R1_001.fastq.gz RNA-Seq 6.5 GB link
— SRR29727685.lite RNA-Seq 834.1 MB link
— WT-1_M_ZHO2261A1-1_S1_L001_R1_001.fastq.gz RNA-Seq 2.7 GB link
— WT-2_M_ZHO2261A2-1_S2_L001_R1_001.fastq.gz RNA-Seq 2.0 GB link
— WT-3_M_ZHO2261A3-1_S3_L001_R1_001.fastq.gz RNA-Seq 834.1 MB link
— WT-LPS-1_M_ZHO2261A4-1_S4_L001_R1_001.fastq.gz RNA-Seq 2.9 GB link
— WT-LPS-2_M_ZHO2261A5-1_S5_L001_R1_001.fastq.gz RNA-Seq 3.9 GB link
— WT-LPS-3_M_ZHO2261A6-1_S6_L001_R1_001.fastq.gz RNA-Seq 3.2 GB link