|
| Status |
Public on Apr 15, 2020 |
| Title |
An integrated multi-omics approach identifies the landscape of interferon-a-mediated responses of human pancreatic beta cells [ATAC-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Proinflammatory cytokines are important mediators of pancreatic beta cell dysfunction and demise in type 1 diabetes (T1D). We presently characterized human beta cell responses to IFNa by combining ATAC-seq, RNA-seq and proteomics assays. The initial beta cell response to IFNa was characterized by major chromatin remodeling, followed by marked changes in transcriptional and translational regulation. IFNa-induced changes in alternative splicing (AS) and first exon usage increased the diversity of transcripts expressed by beta cells. This, combined with changes observed on protein modification/degradation, ER stress and MHC class I, may significantly expand the peptide repertoire presented by beta cells to the immune system. On the other hand, beta cells up-regulated checkpoint proteins, such as PDL1 and HLA-E, that may protect them against the autoimmune assault. Data mining of the present multi-omics analysis led to the identification of two compound classes that revert IFNa effects on human beta cells and may be translated to clinical trials.
|
| |
|
| Overall design |
ATAC-sequencing of 4 independent experiments of the human beta cell line EndoC-BH1 cells exposed or not to intereron-alpha for 2 and 24h.
|
| |
|
| Contributor(s) |
Eizirik DL, Colli ML |
| Citation(s) |
32444635, 33042023, 33281748 |
| |
| Submission date |
Jun 24, 2019 |
| Last update date |
Dec 08, 2020 |
| Contact name |
Maikel Luis Colli |
| E-mail(s) |
mcolli@ulb.ac.be
|
| Organization name |
Universite Libre de Bruxelles
|
| Department |
Faculty of Medicine
|
| Lab |
Center for Diabetes Research
|
| Street address |
Route de Lennik, 808
|
| City |
Brussels |
| ZIP/Postal code |
1070 |
| Country |
Belgium |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (16)
|
| GSM3902499 |
ATAC-seq_Experiment 1 - control condition (2h) |
| GSM3902500 |
ATAC-seq_Experiment 2 - control condition (2h) |
| GSM3902501 |
ATAC-seq_Experiment 3 - control condition (2h) |
| GSM3902502 |
ATAC-seq_Experiment 4 - control condition (2h) |
| GSM3902503 |
ATAC-seq_Experiment 1 - control condition (24h) |
| GSM3902504 |
ATAC-seq_Experiment 2 - control condition (24h) |
| GSM3902505 |
ATAC-seq_Experiment 3 - control condition (24h) |
| GSM3902506 |
ATAC-seq_Experiment 4 - control condition (24h) |
| GSM3902507 |
ATAC-seq_Experiment 1 - Interferon-alpha condition (2h) |
| GSM3902508 |
ATAC-seq_Experiment 2 - Interferon-alpha condition (2h) |
| GSM3902509 |
ATAC-seq_Experiment 3 - Interferon-alpha condition (2h) |
| GSM3902510 |
ATAC-seq_Experiment 4 - Interferon-alpha condition (2h) |
| GSM3902511 |
ATAC-seq_Experiment 1 - Interferon-alpha condition (24h) |
| GSM3902512 |
ATAC-seq_Experiment 2 - Interferon-alpha condition (24h) |
| GSM3902513 |
ATAC-seq_Experiment 3 - Interferon-alpha condition (24h) |
| GSM3902514 |
ATAC-seq_Experiment 4 - Interferon-alpha condition (24h) |
|
| This SubSeries is part of SuperSeries: |
| GSE133221 |
An integrated multi-omics approach identifies the landscape of interferon-a-mediated responses of human pancreatic beta cells |
|
| Relations |
| BioProject |
PRJNA550406 |
| SRA |
SRP211833 |
Less...
More...