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| Status |
Public on Jan 30, 2020 |
| Title |
Stress-induced beta cell dedifferentiation prior to immune cell infiltration prevents type 1 diabetes [Bulk] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Immune-mediated destruction of insulin-producing β-cells causes type 1 diabetes (T1D). However, how β-cells themselves participate in the disease process is poorly understood. Here, we report that modulating the unfolded protein response (UPR) in β-cells of non-obese diabetic (NOD) mice in early stages of disease results in preserved β-cell function, substantially reduced islet immune cell infiltration, and β-cell apoptosis leading to protection from T1D. NOD mice that lack the UPR sensor IRE1α in β-cells show greatly reduced expression of β-cell identity markers, islet autoantigens, and genes involved in antigen presentation. These mice exhibit upregulation of immune inhibitory markers in β-cells and significantly less cytotoxic CD8+ T cells in the pancreas. Our results indicate that triggering transient β-cell dedifferentiation via targeting a specific branch of the UPR in β-cells, prior to insulitis, allow β-cells to escape from immune destruction and may be used as a novel preventive strategy for high-risk individuals.
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| Overall design |
mRNA sequencing of 7-week-old IRE1αfl/fl (WT) and IRE1αβ-/- (KO) mice were done with n=4 per group
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| Contributor(s) |
Lee H, Lee Y, Harenda Q, Pietrzak S, Oktay HZ, Schreiber S, Liao Y, Sonthalia S, Keles S, Sridharan R, Engin F |
| Citation(s) |
32220307 |
| |
| Submission date |
Jan 29, 2020 |
| Last update date |
Apr 30, 2020 |
| Contact name |
Feyza Engin |
| Organization name |
University of Wisconsin-Madison
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| Department |
Biomolecular Chemistry
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| Street address |
440 Henry Mall
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| City |
Madison |
| State/province |
Wisconsin |
| ZIP/Postal code |
53706 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE144472 |
Stress-induced beta cell dedifferentiation prior to immune cell infiltration prevents type 1 diabetes |
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| Relations |
| BioProject |
PRJNA603743 |
| SRA |
SRP245851 |
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