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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 12, 2024 |
| Title |
Expression of the transcription factor HIF-1α in NKp46+ innate lymphoid cells limits inflammation and fibrosis upon chronic colitis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Innate lymphoid cells (ILCs) are critically involved in intestinal adaptation to microenvironmental challenges (Colonna, 2018; Guendel et al., 2020) and the gut mucosa is characterized by low oxygen. Adaptation to low oxygen is mediated by Hypoxia-inducible transcription factors (HIFs) the HIF-1α subunit shapes the ILC phenotype upon acute experimental colitis and contributes to intestinal damage. However, the impact of HIF signaling in NKp46+ ILC in the context of repetitive mucosal damage and chronic inflammation, as it typically occurs during inflammatory bowel disease, is unknown. In a model of chronic colitis, mice lacking the HIF-1α isoform in NKp46+ ILCs show a decrease in NKp46+ ILC1s but a concomitant rise in neutrophils as well as Ly6C high macrophages. Single-nuclei RNA sequencing suggests enhanced interaction of mesenchymal cells with other cell compartments in the colon of HIF-1α KO mice and a loss of mucus-producing enterocytes as well as intestinal stem cells. This was, furthermore, associated with increased BMP-integrin signaling, expansion of profibrotic fibroblasts subsets and intestinal fibrosis. In summary this suggests that HIF-1 α mediated ILC1 activation, although detrimental upon acute colitis, protects against excessive inflammation and fibrosis during chronic intestinal damage.
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| Overall design |
In order to assess the impact of HIF1α-deficiency in NKp46+ cells on the gut microenvironment beyond the immune cell compartment at the whole tissue level and at single-cell resolution, we performed single nuclei RNA sequencing on frozen colon tissue from WT and HIF1α KO mice after chronic DSS exposure.
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| Contributor(s) |
Fan Z, Nelius E, Stockmann C |
| Citation(s) |
38876796 |
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| Submission date |
Jan 05, 2024 |
| Last update date |
Jul 01, 2024 |
| Contact name |
Zheng Fan |
| Organization name |
University of Zurich
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| Department |
Anatomy Institute
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| Street address |
Winterthurerstrasse 190
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| City |
Zurich |
| ZIP/Postal code |
CH-8057 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA1061495 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE252602_RAW.tar |
161.1 Mb |
(http)(custom) |
TAR (of LOOM, MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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