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| Status |
Public on Sep 20, 2019 |
| Title |
The impact of pro-inflammatory cytokines on the β-cell regulatory landscape provides insights into the genetics of type 1 diabetes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Early stages of type 1 diabetes (T1D) are characterized by local autoimmune inflammation and progressive loss of insulin-producing pancreatic β cells. We show here that exposure to pro-inflammatory cytokines unmasks a marked plasticity of the β-cell regulatory landscape. We expand the repertoire of human islet regulatory elements by mapping stimulus-responsive enhancers linked to changes in the β-cell transcriptome, proteome and 3D chromatin structure. Our data indicates that the β cell response to cytokines is mediated by the induction of novel regulatory regions as well as the activation of primed regulatory elements pre-bound by islet-specific transcription factors. We found that T1D-associated loci are enriched of the newly mapped cis-regulatory regions and identify T1D-associated variants disrupting cytokine-responsive enhancer activity in human β cells. Our study illustrates how β cells respond to a pro-inflammatory environment and implicate a role for stimulus-response islet enhancers in T1D.
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| |
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| Overall design |
Five independent preparations of EndoC-βH1 cells examined under 2 conditions (control and pro-inflammatory cytokine exposure)
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| |
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| Contributor(s) |
Ramos-Rodríguez M, Turatsinze J, Pasquali L, Eizirik DL |
| Citation(s) |
33281748, 36287121 |
| |
| Submission date |
Sep 09, 2019 |
| Last update date |
Nov 02, 2022 |
| Contact name |
Mireia Ramos-Rodríguez |
| E-mail(s) |
mramos@igtp.cat
|
| Phone |
+34 93 557 28 13
|
| Organization name |
Germans Trias i Pujol University Hospital and Research Institute
|
| Department |
Division of Endocrinology
|
| Lab |
Endocrine Regulatory Genomics Laboratory
|
| Street address |
Carretera de Can Ruti, camí de les escoles s/n
|
| City |
Badalona |
| ZIP/Postal code |
08916 |
| Country |
Spain |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (10)
|
| GSM4067526 |
EndoC-βH1 cells preparation 1 under control condition |
| GSM4067527 |
EndoC-βH1 cells preparation 1 under cytokine treatment |
| GSM4067528 |
EndoC-βH1 cells preparation 2 under control condition |
| GSM4067529 |
EndoC-βH1 cells preparation 2 under cytokine treatment |
| GSM4067530 |
EndoC-βH1 cells preparation 3 under control condition |
| GSM4067531 |
EndoC-βH1 cells preparation 3 under cytokine treatment |
| GSM4067532 |
EndoC-βH1 cells preparation 4 under control condition |
| GSM4067533 |
EndoC-βH1 cells preparation 4 under cytokine treatment |
| GSM4067534 |
EndoC-βH1 cells preparation 5 under control condition |
| GSM4067535 |
EndoC-βH1 cells preparation 5 under cytokine treatment |
|
| Relations |
| BioProject |
PRJNA564614 |
| SRA |
SRP221142 |
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