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Series GSE145829 Query DataSets for GSE145829
Status Public on Aug 24, 2020
Title Ileum/colon treated with succinate
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 WT Ileum or Colon Biological Replicates Collected from WT Mice treated with succinate
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)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (5)
GSM4336576 succinate_terminal ileum [4171_2]
GSM4336577 succinate_terminal ileum [4171_6]
GSM4336578 succinate_terminal ileum [4171_9]
This SubSeries is part of SuperSeries:
GSE145830 Ileal single-cell analysis in the context of inflammation focused on tuft cells
BioProject PRJNA608465
SRA SRP250540

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
GSE145829_RAW.tar 13.9 Mb (http)(custom) TAR (of CSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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