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| Status |
Public on Sep 18, 2020 |
| Title |
IRF2 maintains the stemness of colonic stem cells by limiting physiological stress from interferon |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The physiological stresses that diminish tissue stem-cell characteristics remain largely unknown. We previously reported that type I interferon (IFN), which is essential for host antiviral responses, is a physiological stressor for hematopoietic stem cells (HSCs) and that interferon regulatory factor-2 (IRF2), which attenuates IFN signaling, maintains the stemness of HSCs. Here, we explore the role of IRF2 in maintaining colonic epithelial stem cells (CoSCs). In mice with a conditional Irf2 deletion in the intestinal epithelium (hereafter Irf2ΔIEC mice), both the number and the organoid-forming potential of CoSCs was markedly reduced. Consistent with this finding, the ability of Irf2ΔIEC mice to regenerate colon epithelium after injury by dextran sodium sulfate (DSS) was severely impaired, independently of microbial dysbiosis. Mechanistically, CoSCs differentiated prematurely into transit-amplifying (TA) cells in Irf2ΔIEC mice, which might explain their low CoSC counts. A similar phenotype was induced in wild-type mice by repeated injections of low doses of poly(I:C), which induces type I IFN. Collectively, we demonstrated that chronic IFN signaling physiologically stresses CoSCs. This study provides new insight into the molecular mechanisms that maintain functional CoSCs throughout life.
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| Overall design |
To identify the differentially regulated biological process that accounts for the reduction of CoSCs in Irf2ΔIEC mice, we performed microarray of sorted colonic crypt epithelial cells from naïve Irf2ΔIEC and Irf2fl/fl control mice.
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| Contributor(s) |
Minamide K, Sato T, Nakanishi Y, Asano J, Ohno H, Kato T, Ohteki T |
| Citation(s) |
32901054 |
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https://0-doi-org.brum.beds.ac.uk/10.1038/s41598-020-71633-3
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| Submission date |
Nov 20, 2017 |
| Last update date |
Oct 02, 2020 |
| Contact name |
Kana MINAMIDE |
| E-mail(s) |
kananm.bre@mri.tmd.ac.jp
|
| Organization name |
Tokyo Medical and Dental University
|
| Department |
Medical Research Institute
|
| Lab |
Laboratory of Biodefence research
|
| Street address |
1-5-45
|
| City |
Bunkyo-ku |
| State/province |
Tokyo |
| ZIP/Postal code |
113-8510 |
| Country |
Japan |
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| Platforms (1) |
| GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
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| Samples (2) |
| GSM2861660 |
Colon_crypt_epithelial_cell_naive_control |
| GSM2861661 |
Colon_crypt_epithelial_cell_naive_cKO |
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| Relations |
| BioProject |
PRJNA419153 |
