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Series GSE102371 Query DataSets for GSE102371
Status Public on Jul 30, 2018
Title Functional Genomics Analysis of Islets from Recent and Longstanding T1D Reveals the Need for Distinct Approaches to Therapy
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Our current understanding of the pathogenesis of T1D arose in large part from studies using the non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D). Of concern, therapeutic interventions shown to significantly dampen or even reverse disease in mouse models have not successfully translated into interventions in human T1D. The present study addresses this disconnect in research translation by directly analyzing human donor islets from individuals with T1D, aiming to provide insight into disease mechanisms and identify potential target pathways for therapeutic intervention. We obtained human islets from a young individual with short-duration T1D, an older individual with long-duration T1D and three non-diabetic donors, and performed unbiased functional genomic analysis by high depth RNA sequencing on these unique cases. This analysis identified several inflammatory pathways upregulated in short-duration disease, which surprisingly included many components of innate immunity. Subsequent manipulation of one of these pathways/factors in NOD mice resulted in a significant reduction in diabetes progression when inhibition occurred early in disease progression. Taken together our data demonstrates that the direct analysis of human islets is essential for identifying relevant and promising novel targets for translation into effective therapeutic interventions for human T1D.
Overall design 5 human islets of Langerrhans preparations. 3 in normo-glycemic individual, one individual with a long duration type 1 diabetes and one individual with short duration type 1 diabetes
Contributor(s) Mastracci TL, Turatsinze J, Eizirik DL, Mirmira RG
Citation(s) 29569324
Submission date Aug 08, 2017
Last update date Jul 25, 2021
Contact name Teresa L. Mastracci
Organization name Indiana Biosciences Research Institute
Street address 1345 W. 16th St., Suite 300,
City Indianapolis
ZIP/Postal code 46202
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (5)
GSM2735597 islet preparation from normo-glycemic individual 1
GSM2735598 islet preparation from normo-glycemic individual 2
GSM2735599 islet preparation from normo-glycemic individual 3
BioProject PRJNA397581
SRA SRP115040

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Supplementary file Size Download File type/resource
GSE102371_RAW.tar 19.7 Mb (http)(custom) TAR (of GTF)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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