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| Status |
Public on Sep 14, 2022 |
| Title |
Transcription and splicing regulation by NLRC5 shape the interferon response in human pancreatic β-cells [iPSC scRNAseq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
IFNa is a key regulator of the dialogue between pancreatic β-cells and the immune system in early type 1 diabetes (T1D). IFNa up-regulates HLA class I expression in human β-cells fostering autoantigen presentation to the immune system. We observed by bulk and single cell RNA sequencing that exposure of human induced pluripotent-derived islet-like cells to IFNa induces expression of HLA class I and of other genes involved in antigen presentation, including the transcriptional activator NLRC5. We next evaluated the global role of NLRC5 in human insulin-producing EndoC-βH1 and human islets cells by RNA sequencing and targeted gene/protein determination. NLRC5 regulates expression of HLA class I expression and related genes and of chemokines. NLRC5 also mediates the effects of IFNa on alternative splicing, a generator of β-cell neoantigens, suggesting that it is a central mediator of the effects of IFNa on β-cells that contribute to trigger and amplify autoimmunity in T1D.
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| Overall design |
Comparative gene expression profiling analysis of scRNA-seq data for Islets-like cells exposed, or not, to IFNa
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| Contributor(s) |
Szymczak F, Alvelos MI, Marín-Cañas S, Castela Â, Eizirik DL |
| Citation(s) |
36103539 |
| |
| Submission date |
May 19, 2022 |
| Last update date |
Oct 06, 2022 |
| Contact name |
Florian Szymczak |
| Organization name |
Université Libre de Bruxelles
|
| Department |
Faculty of Medicine
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| Lab |
ULB Center for Diabetes Research
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| Street address |
Route de Lennik 808 - CP618
|
| City |
Anderlecht |
| State/province |
Brussels |
| ZIP/Postal code |
1070 |
| Country |
Belgium |
| |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE203385 |
Transcription and splicing regulation by NLRC5 shape the interferon response in human pancreatic β-cells |
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| Relations |
| BioProject |
PRJNA839716 |
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