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| Status |
Public on Sep 22, 2018 |
| Title |
Human Pancreatic Islets Expressing HNF1A Variant Have Defective β cell Transcriptional Regulatory Networks |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Using an integrated approach to characterize the pancreatic tissue and isolated islets from a 33-year-old with 17 years of type 1 diabetes (T1D), we found donor islets contained β cells without insulitis and lacked glucose-stimulated insulin secretion despite a normal insulin response to cAMP-evoked stimulation. With these unexpected findings for T1D, we sequenced the donor DNA and found a pathogenic heterozygous variant in hepatocyte nuclear factor 1 alpha (HNF1A). In one of the first studies of human pancreatic islets with a disease-causing HNF1A variant associated with the most common form of monogenic diabetes, we found that HNF1A dysfunction leads to insulin-insufficient diabetes reminiscent of T1D by impacting the regulatory processes critical for glucose-stimulated insulin secretion and suggest a rationale for a therapeutic alternative to current treatment.
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| Overall design |
Total of 12 samples were analyzed, 10 were non-diabetic control donors and 2 were HNF1A donors. GEO accession number for non-diabetic controls are GSE116559(β cell controls) and GSE106148 (α cell controls). α cells and β cells were FACS-sorted and RNA was extracted from each of these samples. RNAseq was performed on all 12 samples
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| Contributor(s) |
Powers AC, Haliyur R |
| Citation(s) |
30507613 |
| |
| Submission date |
Sep 21, 2018 |
| Last update date |
Oct 28, 2020 |
| Contact name |
NRIPESH PRASAD |
| E-mail(s) |
nprasad@hudsonalpha.org
|
| Phone |
2563279413
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| Organization name |
HUDSONALPHA INSTITUTE FOR BIOTECHNOLOGY
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| Department |
GENOMIC SERVICES LABORATORY
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| Street address |
601 GENOME WAY
|
| City |
HUNTSVILLE |
| State/province |
AL |
| ZIP/Postal code |
35806 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA492458 |
| SRA |
SRP162332 |
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