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Series GSE184359 Query DataSets for GSE184359
Status Public on Oct 21, 2022
Title Loss of autism-candidate CHD8 perturbs neural crest development and intestinal homeostatic balance [RNA-seq]
Organism Danio rerio
Experiment type Expression profiling by high throughput sequencing
Summary Individuals with mutations in CHD8 present with gastrointestinal complaints, yet the underlying mechanisms are understudied. Here, utilizing a stable constitutive chd8 mutant zebrafish model, we found that the loss of chd8 leads to reduced number of vagal neural crest cells (NCCs), enteric neural and glial progenitors, emigrating from the neural tube and that their early migration capability was altered. At later stages, although the intestinal colonization by the NCCs was complete, we found decreased numbers of both serotonin-producing enterochromaffin cells and NCC-derived serotonergic neurons, suggesting an intestinal hyposerotonemia in absence of chd8. Further, transcriptomic analyses revealed altered expression of key receptors and enzymes in serotonin and acetylcholine signaling pathways. Tissue examination of chd8 mutants revealed thinner intestinal epithelium accompanied by accumulation of neutrophils and decreased numbers of goblet cells and eosinophils. Last, single-cell sequencing of whole intestines showed a global disruption of the immune balance with perturbed expression of inflammatory interleukins and changes in immune cell clusters. Our findings propose a causal developmental link between chd8, NCC development, intestinal homeostasis, and autism-associated gastrointestinal complaints.
 
Overall design 8 samples were analyzed: 4 tg(phox2bb:GFP);chd8+/+ (wild-type) and 4 tg(phox2bb:GFP);chd8sa19827/+ (heterozygous mutants). Each sample is comprised of a clutch of at least 80 4 days post-fertilization larvae.
 
Contributor(s) Hayot G, Massonot M, Keime C, Faure E, Golzio C
Citation(s)
  • Hayot G, Massonot M, Keime C, Faure E et al. Loss of autism-candidate CHD8 perturbs neural crest development and intestinal homeostatic balance. Life Sci Alliance 2023 Jan;6(1). PMID: 36375841
Submission date Sep 17, 2021
Last update date Dec 01, 2022
Contact name Christelle Golzio
E-mail(s) christelle.golzio@inserm.fr
Organization name IGBMC
Street address 1 rue Laurent Fries
City Illkirch
State/province Alsace
ZIP/Postal code 67400
Country France
 
Platforms (1)
GPL21741 Illumina HiSeq 4000 (Danio rerio)
Samples (8)
GSM5585062 chd8+/+ 4dpf eNCC #1
GSM5585063 chd8+/+ 4dpf eNCC #2
GSM5585064 chd8+/+ 4dpf eNCC #3
This SubSeries is part of SuperSeries:
GSE184364 Loss of autism-candidate CHD8 perturbs neural crest development and intestinal homeostatic balance
Relations
BioProject PRJNA764215
SRA SRP337626

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE184359_merged_htseqcount.tsv.gz 413.5 Kb (ftp)(http) TSV
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Raw data are available in SRA
Processed data are available on Series record

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