Comment[ArrayExpressAccession]	E-GEOD-47720
MAGE-TAB Version	1.1									
Public Release Date	2013-06-07
Investigation Title	miRNA-sequencing of human pancreatic islets and enriched beta-cells									
Comment[Submitted Name]	miRNA-sequencing of human pancreatic islets and enriched beta-cells
Experiment Description	Recent advances in the understanding of the genetics of type 2 diabetes (T2D) susceptibility have focused attention on the regulation of transcriptional activity within the pancreatic beta-cell. MicroRNAs (miRNAs) represent an important component of regulatory control, and have proven roles in the development of human disease and control of glucose homeostasis. We set out to establish the miRNA profile of human pancreatic islets and of enriched beta-cell populations, and to explore their potential involvement in T2D susceptibility. We used Illumina small RNA sequencing to profile the miRNA fraction in three preparations each of primary human islets and of enriched beta-cells generated by fluorescence-activated cell sorting. In total, 366 miRNAs were found to be expressed (i.e. >100 cumulative reads) in islets and 346 in beta-cells; of the total of 384 unique miRNAs, 328 were shared. A comparison of the islet-cell miRNA profile with those of 15 other human tissues identified 40 miRNAs predominantly expressed (i.e. >50% of all reads seen across the tissues) in islets. Several highly-expressed islet miRNAs, such as miR-375, have established roles in the regulation of islet function, but others (e.g. miR-27b-3p, miR-192-5p) have not previously been described in the context of islet biology. As a first step towards exploring the role of islet-expressed miRNAs and their predicted mRNA targets in T2D pathogenesis, we looked at published T2D association signals across these sites. We found evidence that predicted mRNA targets of islet-expressed miRNAs were globally enriched for signals of T2D association (p-values <0.01, q-values <0.1). At six loci with genome-wide evidence for T2D association (AP3S2, KCNK16, NOTCH2, SCL30A8, VPS26A, and WFS1) predicted mRNA target sites for islet-expressed miRNAs overlapped potentially causal variants. In conclusion, we have described the miRNA profile of human islets and beta-cells and provide evidence linking islet miRNAs to T2D pathogenesis. Examination of the miRNA profiles in 3 preparations of isolated pancreatic islets and 3 preparations of FACS-enriched pancreatic beta-cells									
Term Source Name	ArrayExpress	EFO
Term Source File	http://www.ebi.ac.uk/arrayexpress/	http://www.ebi.ac.uk/efo/efo.owl								
Person Last Name	van de Bunt	van de Bunt	Gaulton	Parts	Morán	Johnson	Lindgren	Ferrer	Gloyn	McCarthy
Person First Name	Martijn	Martijn	Kyle	Leopold	Ignasi	Paul	Cecilia	Jorge	Anna	Mark
Person Mid Initials			J			R	M		L	I
Person Email	geo@ncbi.nlm.nih.gov									
Person Affiliation	Oxford Centre for Diabetes, Metabolism & Endocrinology									
Person Address	Oxford Centre for Diabetes, Metabolism & Endocrinology, OCDEM, Churchill Hospital, Headington, Oxford, United Kingdom									
Person Roles	submitter									
Protocol Name	P-GSE47720-1									
Protocol Description	total RNA extracted using Trizol solution Illumina v1.5 or TruSeq v1 small RNA library protocol									
Protocol Type	nucleic acid library construction protocol									
Experimental Factor Name	BMI	PURITY	SEX	AGE						
Experimental Factor Type	bmi	purity	Sex	age						
Publication Title	The miRNA profile of human pancreatic islets and beta-cells and relationship to type 2 diabetes pathogenesis.									
Publication Author List	van de Bunt M, Gaulton KJ, Parts L, Moran I, Johnson PR, Lindgren CM, Ferrer J, Gloyn AL, McCarthy MI									
PubMed ID	23372846									
Publication DOI	10.1371/journal.pone.0055272									
Comment[SecondaryAccession]	GSE47720									
Comment[GEOReleaseDate]	2013-06-07									
Comment[ArrayExpressSubmissionDate]	2013-06-06									
Comment[GEOLastUpdateDate]	2013-06-10									
Comment[AEExperimentType]	RNA-seq of non coding RNA									
Comment[AdditionalFile:Data1]	GSE47720_miRNA_normalized_counts_all.txt									
Comment[SecondaryAccession]	SRP023531									
SDRF File	E-GEOD-47720.sdrf.txt