GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE145827 Query DataSets for GSE145827
Status Public on Aug 24, 2020
Title WT/AtohKO/TNFdARE Ileum
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary An inverse correlation between countries endemic for helminth infestation and Crohn's disease (CD) incidences has been reinforced by anecdotal but successful cases of helminth therapy for CD. Recent studies have revealed that tuft cells in the small intestine are critical for sensing helminths and directing a type 2 immune response to counteract colonization. Here, we establish an inverse relationship between chemosensory tuft cells and local tissue inflammation in CD patients as well as an established mouse model of TNF-á-induced Crohn's-like ileitis (TNFÄARE). Using a combination of mouse and organoid models, single-cell RNA-sequencing, multiplex immunofluorescence, computational analysis, metabolite mass spectrometry, and microbiome sequencing and manipulation, we identified Atonal Homolog 1 (ATOH1)-independent tuft cells, as opposed to ATOH1-dependent tuft cells, to be responsive to the commensal microbiome through the tricarboxylic acid (TCA) cycle metabolite succinate. To evaluate the ability of the malleable, ATOH1-independent tuft cell population to suppress intestinal inflammation, we administered succinate to TNFÄARE animals post onset of ileal inflammatory disease. We observed significantly reduced pathology that is exquisitely dependent on succinate-induced tuft cell specification in the disease model, leading to an anti-helminth response previously shown to suppress inflammation. Inflammation suppression was triggered by cytokines critical to anti-helminthic response, such as IL-22, IL-25, and IL-13. We provide evidence implicating the modulatory role of intestinal tuft cells in chronic intestinal inflammation, which could enable the development of CD therapies around leveraging this rare and elusive cell type.
Overall design Ileum Biological Replicates Collected from WT/AtohKO/TNFdARE Mice; 7 WT vs. 3 AtohKO vs. 3 TNFdARE
Contributor(s) Lau K, Banerjee A, Simmons AJ
Citation(s) 32828819
Submission date Feb 24, 2020
Last update date Aug 29, 2020
Contact name Ken Lau
Phone 6159366859
Organization name Vanderbilt University
Department Cell and Developmental Biology
Street address 2215 Garland Ave. MRBIV10475
City Nashville
State/province TN
ZIP/Postal code 37232
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (14)
GSM4336558 wt1
GSM4336559 wt2
GSM4336560 wt3
This SubSeries is part of SuperSeries:
GSE145830 Ileal single-cell analysis in the context of inflammation focused on tuft cells
BioProject PRJNA608463
SRA SRP250538

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
GSE145827_RAW.tar 32.0 Mb (http)(custom) TAR (of CSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap