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| Status |
Public on Jan 14, 2021 |
| Title |
Single-cell chromatin accessibility identifies pancreatic islet cell type- and state-specific regulatory programs of diabetes risk [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq) creates new opportunities to dissect cell type-specific mechanisms of complex diseases. Since pancreatic islets are central to type 2 diabetes (T2D), we profiled 15,298 islet cells by using combinatorial barcoding snATAC-seq and identified 12 clusters, including multiple alpha, beta and delta cell states. We cataloged 228,873 accessible chromatin sites and identified transcription factors underlying lineage- and state-specific regulation. We observed state-specific enrichment of fasting glucose and T2D genome-wide association studies for beta cells and enrichment for other endocrine cell types. At T2D signals localized to islet-accessible chromatin, we prioritized variants with predicted regulatory function and co-accessibility with target genes. A causal T2D variant rs231361 at the KCNQ1 locus had predicted effects on a beta cell enhancer co-accessible with INS and genome editing in embryonic stem cell-derived beta cells affected INS levels. Together our findings demonstrate the power of single-cell epigenomics for interpreting complex disease genetics.
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| |
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| Overall design |
RNA-seq of ES-derived beta cells with KCNQ1enh deletion (n=6; 3 clones each differentiated two times) and scrambled control (n=2; 1 clone differentiated two times).
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| |
|
| Contributor(s) |
Chiou J, Gaulton KJ |
| Citation(s) |
33795864 |
| |
| Submission date |
Oct 29, 2020 |
| Last update date |
Apr 15, 2021 |
| Contact name |
Kyle Gaulton |
| E-mail(s) |
kgaulton@health.ucsd.edu
|
| Organization name |
University of California, San Diego
|
| Department |
Pediatrics
|
| Lab |
Gaulton Lab
|
| Street address |
9500 Gilman Drive
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
|
| Samples (8)
|
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| This SubSeries is part of SuperSeries: |
| GSE160474 |
Single-cell chromatin accessibility identifies pancreatic islet cell type- and state-specific regulatory programs of diabetes risk |
|
| Relations |
| BioProject |
PRJNA673283 |
| SRA |
SRP289943 |
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