GSE271650
GSE GEOAutism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes [bulk RNA-seq]
Organism:
Mus musculus
Platform:
GPL24247
Samples:
18
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/PRJNA1132694
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 GSE271650
- Adapter sequences, low base call quality (Phred score <30), and reads with fewer than 5 bases, were trimmed from all FASTQ files using Cutadapt (v3.5)
- STAR (Dobin et al., Bioinformatics, 2012, DOI: 10.1093/bioinformatics/bts635) aligner was used to align trimmed sequences to the mouse reference genome (GRCm39) with gene annotations from mouse Gencode (vM28)
- Gene count quantifications were analyzed using RSEM (RNA-Seq by Expectation Maximization; v.1.3.1)
- Expected gene count quantifications from RSEM analysis were imported into R for differential gene analysis using edgeR (v.3.30.3)
- Functional pathway analysis was performed using Metascape (Zhou et al., Nature Communications, 2019, DOI: 10.1038/s41467-019-09234-6), gProfiler (Reimand et al., R package version 0.67, 2018; https://cran.r-project.org/web/packages/gProfileR/gProfileR.pdf), and ClusterProfiler
Supplementary Files (3)
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 (18) and Runs (18)
Total: 55348 MBGSM8381189: Cortex, Saline, 3days, Control Saline Sample 1; Mus musculus; RNA-Seq
Sample: SRS21916282
BioProject: PRJNA1132694
BioSample: SAMN42353231
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
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 |
|---|---|---|---|---|---|
| SRR29727678 | 71994160 | 14542820320 | 4507.77 | Yang_Zhou_sample1_2-2136355_S1_L002_R1_001.fastq.gz, Yang_Zhou_sample… | SRA |
GSM8381190: Cortex, Saline, 3days, Control Saline Sample 3; Mus musculus; RNA-Seq
Sample: SRS21916283
BioProject: PRJNA1132694
BioSample: SAMN42353230
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
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 |
|---|---|---|---|---|---|
| SRR29727677 | 57791264 | 11673835328 | 3618.73 | Yang_Zhou_sample3_2-2136357_S3_L002_R1_001.fastq.gz, Yang_Zhou_sample… | SRA |
GSM8381191: Cortex, Saline, 3days, Control Saline Sample 5; Mus musculus; RNA-Seq
Sample: SRS21916284
BioProject: PRJNA1132694
BioSample: SAMN42353229
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
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 |
|---|---|---|---|---|---|
| SRR29727676 | 51135694 | 10329410188 | 3221.58 | Yang_Zhou_sample5_2-2136359_S5_L002_R1_001.fastq.gz, Yang_Zhou_sample… | SRA |
GSM8381192: Cortex, Saline, 3days, Control Saline Sample 7; Mus musculus; RNA-Seq
Sample: SRS21916285
BioProject: PRJNA1132694
BioSample: SAMN42353228
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
genotype: Control Saline 4
treatment: Saline
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727675 | 53254425 | 10757393850 | 3305.9 | Yang_Zhou_sample7_2-2136361_S7_L002_R1_001.fastq.gz, Yang_Zhou_sample… | SRA |
GSM8381193: Cortex, Saline, 3days, cKO Saline Sample 2; Mus musculus; RNA-Seq
Sample: SRS21916286
BioProject: PRJNA1132694
BioSample: SAMN42353227
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
genotype: Astrocyte cKO Saline 1
treatment: Saline
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727674 | 50033081 | 10106682362 | 3220.43 | Yang_Zhou_sample2_2-2136356_S2_L002_R1_001.fastq.gz, Yang_Zhou_sample… | SRA |
GSM8381194: Cortex, Saline, 3days, cKO Saline Sample 4; Mus musculus; RNA-Seq
Sample: SRS21916288
BioProject: PRJNA1132694
BioSample: SAMN42353226
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
genotype: Astrocyte cKO Saline 2
treatment: Saline
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727673 | 51675489 | 10438448778 | 3220.55 | Yang_Zhou_sample4_2-2136358_S4_L002_R1_001.fastq.gz, Yang_Zhou_sample… | SRA |
GSM8381195: Cortex, Saline, 3days, cKO Saline Sample 6; Mus musculus; RNA-Seq
Sample: SRS21916287
BioProject: PRJNA1132694
BioSample: SAMN42353225
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
genotype: Astrocyte cKO Saline 3
treatment: Saline
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727672 | 52981230 | 10702208460 | 3321.93 | Yang_Zhou_sample6_2-2136360_S6_L002_R1_001.fastq.gz, Yang_Zhou_sample… | SRA |
GSM8381196: Cortex, Saline, 3days, cKO Saline Sample 8; Mus musculus; RNA-Seq
Sample: SRS21916289
BioProject: PRJNA1132694
BioSample: SAMN42353224
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
genotype: Astrocyte cKO Saline 4
treatment: Saline
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727671 | 45684935 | 9228356870 | 2852.06 | Yang_Zhou_sample8_2-2136362_S8_L002_R1_001.fastq.gz, Yang_Zhou_sample… | SRA |
GSM8381197: Cortex, Saline, 3days, Control LPS Sample A1; Mus musculus; RNA-Seq
Sample: SRS21916290
BioProject: PRJNA1132694
BioSample: SAMN42353223
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
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 |
|---|---|---|---|---|---|
| SRR29727670 | 50420447 | 10184930294 | 3068.98 | Zhou_A1_2-2322646_S1_L001_R1_001.fastq.gz, Zhou_A1_2-2322646_S1_L001_… | SRA |
GSM8381198: Cortex, Saline, 3days, Control LPS Sample B2; Mus musculus; RNA-Seq
Sample: SRS21916291
BioProject: PRJNA1132694
BioSample: SAMN42353222
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
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 |
|---|---|---|---|---|---|
| SRR29727669 | 24757243 | 5000963086 | 1496.53 | Zhou_B2_2-2322647_S2_L001_R1_001.fastq.gz, Zhou_B2_2-2322647_S2_L001_… | SRA |
GSM8381199: Cortex, Saline, 3days, Control LPS Sample C3; Mus musculus; RNA-Seq
Sample: SRS21916292
BioProject: PRJNA1132694
BioSample: SAMN42353221
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
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 |
|---|---|---|---|---|---|
| SRR29727668 | 28754758 | 5808461116 | 1751.08 | Zhou_C3_2-2322648_S3_L001_R1_001.fastq.gz, Zhou_C3_2-2322648_S3_L001_… | SRA |
GSM8381200: Cortex, Saline, 3days, Control LPS Sample K11; Mus musculus; RNA-Seq
Sample: SRS21916293
BioProject: PRJNA1132694
BioSample: SAMN42353220
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
genotype: Control LPS 4
treatment: Lipopolysaccharide
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727667 | 65910723 | 13313966046 | 4052.28 | K11_2-2447630_S1_L001_R1_001.fastq, K11_2-2447630_S1_L001_R2_001.fast… | SRA |
GSM8381201: Cortex, Saline, 3days, Control LPS Sample L12; Mus musculus; RNA-Seq
Sample: SRS21916294
BioProject: PRJNA1132694
BioSample: SAMN42353219
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
genotype: Control LPS 5
treatment: Lipopolysaccharide
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727666 | 22763256 | 4598177712 | 1411.14 | L12_2-2447631_S2_L001_R1_001.fastq, L12_2-2447631_S2_L001_R2_001.fast… | SRA |
GSM8381202: Cortex, Saline, 3days, cKO LPS Sample D4; Mus musculus; RNA-Seq
Sample: SRS21916295
BioProject: PRJNA1132694
BioSample: SAMN42353218
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
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 |
|---|---|---|---|---|---|
| SRR29727665 | 28447731 | 5746441662 | 1724.43 | Zhou_D4_2-2322649_S4_L001_R1_001.fastq.gz, Zhou_D4_2-2322649_S4_L001_… | SRA |
GSM8381203: Cortex, Saline, 3days, cKO LPS Sample E5; Mus musculus; RNA-Seq
Sample: SRS21916296
BioProject: PRJNA1132694
BioSample: SAMN42353217
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
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 |
|---|---|---|---|---|---|
| SRR29727664 | 36816090 | 7436850180 | 2225.84 | Zhou_E5_2-2322650_S5_L001_R1_001.fastq.gz, Zhou_E5_2-2322650_S5_L001_… | SRA |
GSM8381204: Cortex, Saline, 3days, cKO LPS Sample F6; Mus musculus; RNA-Seq
Sample: SRS21916297
BioProject: PRJNA1132694
BioSample: SAMN42353216
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
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 |
|---|---|---|---|---|---|
| SRR29727663 | 37020968 | 7478235536 | 2256.1 | Zhou_F6_2-2322701_S6_L001_R1_001.fastq.gz, Zhou_F6_2-2322701_S6_L001_… | SRA |
GSM8381205: Cortex, Saline, 3days, cKO LPS Sample M13; Mus musculus; RNA-Seq
Sample: SRS21916299
BioProject: PRJNA1132694
BioSample: SAMN42353215
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
genotype: Astrocyte cKO LPS 4
treatment: Lipopolysaccharide
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727662 | 49339096 | 9966497392 | 3055.21 | M13_2-2447632_S3_L001_R1_001.fastq, M13_2-2447632_S3_L001_R2_001.fast… | SRA |
GSM8381206: Cortex, Saline, 3days, cKO LPS Sample N14; Mus musculus; RNA-Seq
Sample: SRS21916298
BioProject: PRJNA1132694
BioSample: SAMN42353214
Platform: ILLUMINA
Instrument: Illumina NovaSeq 6000
Organism: Mus musculus
Sample attributes
source_name: Cortex
tissue: Cortex
cell type: bulk
genotype: Astrocyte cKO LPS 5
treatment: Lipopolysaccharide
geo_loc_name: missing
collection_date: missing
Original files (1)
Cortex
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR29727661 | 113748247 | 22977145894 | 7037.3 | N14_2-2447633_S4_L001_R1_001.fastq, N14_2-2447633_S4_L001_R2_001.fast… | SRA |
Linked Publications (2)
Data Files (18)
| Accession | File Name | Stored Type | Output Type | Mapping Assembly | Size | Download | |
|---|---|---|---|---|---|---|---|
| — | K11_2-2447630_S1_L001_R1_001.fastq | RNA-Seq | 4.0 GB | link | |||
| — | L12_2-2447631_S2_L001_R1_001.fastq | RNA-Seq | 1.4 GB | link | |||
| — | M13_2-2447632_S3_L001_R1_001.fastq | RNA-Seq | 3.0 GB | link | |||
| — | N14_2-2447633_S4_L001_R1_001.fastq | RNA-Seq | 6.9 GB | link | |||
| — | Yang_Zhou_sample1_2-2136355_S1_L002_R1_001.fastq.gz | RNA-Seq | 4.4 GB | link | |||
| — | Yang_Zhou_sample2_2-2136356_S2_L002_R1_001.fastq.gz | RNA-Seq | 3.1 GB | link | |||
| — | Yang_Zhou_sample3_2-2136357_S3_L002_R1_001.fastq.gz | RNA-Seq | 3.5 GB | link | |||
| — | Yang_Zhou_sample4_2-2136358_S4_L002_R1_001.fastq.gz | RNA-Seq | 3.1 GB | link | |||
| — | Yang_Zhou_sample5_2-2136359_S5_L002_R1_001.fastq.gz | RNA-Seq | 3.1 GB | link | |||
| — | Yang_Zhou_sample6_2-2136360_S6_L002_R1_001.fastq.gz | RNA-Seq | 3.2 GB | link | |||
| — | Yang_Zhou_sample7_2-2136361_S7_L002_R1_001.fastq.gz | RNA-Seq | 3.2 GB | link | |||
| — | Yang_Zhou_sample8_2-2136362_S8_L002_R1_001.fastq.gz | RNA-Seq | 2.8 GB | link | |||
| — | Zhou_A1_2-2322646_S1_L001_R1_001.fastq.gz | RNA-Seq | 3.0 GB | link | |||
| — | Zhou_B2_2-2322647_S2_L001_R1_001.fastq.gz | RNA-Seq | 1.5 GB | link | |||
| — | Zhou_C3_2-2322648_S3_L001_R1_001.fastq.gz | RNA-Seq | 1.7 GB | link | |||
| — | Zhou_D4_2-2322649_S4_L001_R1_001.fastq.gz | RNA-Seq | 1.7 GB | link | |||
| — | Zhou_E5_2-2322650_S5_L001_R1_001.fastq.gz | RNA-Seq | 2.2 GB | link | |||
| — | Zhou_F6_2-2322701_S6_L001_R1_001.fastq.gz | RNA-Seq | 2.2 GB | link |