Transcriptomics,Genomics

Dataset Information

30

Human Pancreatic Islets Expressing HNF1A Variant Have Defective β cell Transcriptional Regulatory Networks


ABSTRACT: 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. 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

REANALYSIS of: GSE116559GSE106148

INSTRUMENT(S): Illumina HiSeq 2500 (Homo sapiens)

SUBMITTER: NRIPESH PRASAD  

PROVIDER: GSE120299 | GEO | 2018-09-22

REPOSITORIES: GEO

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