Dataset Information

Cell Type-Selective Expression of Circular RNAs in Human Pancreatic Islets.

ABSTRACT: Understanding distinct cell-type specific gene expression in human pancreatic islets is important for developing islet regeneration strategies and therapies to improve ?-cell function in type 1 diabetes (T1D). While numerous transcriptome-wide studies on human islet cell-types have focused on protein-coding genes, the non-coding repertoire, such as long non-coding RNA, including circular RNAs, remains mostly unexplored. Here, we explored transcriptional landscape of human ?-, ?-, and exocrine cells from published total RNA sequencing (RNA-seq) datasets to identify circular RNAs (circRNAs). Our analysis revealed that circRNAs are highly abundant in both ?- and ?-cells. We identified 10,830 high-confidence circRNAs expressed in human ?-, ?-, and exocrine cells. The most highly expressed candidates were MAN1A2, RMST, and HIPK3 across the three cell-types. Alternate circular isoforms were observed for circRNAs in the three cell-types, indicative of potential distinct functions. Highly selective ?- and ?-cell circRNAs were identified, which is suggestive of their potential role in regulating ?-cell function.

SUBMITTER: Kaur S

PROVIDER: S-EPMC6316812 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Cell Type-Selective Expression of Circular RNAs in Human Pancreatic Islets.

Kaur Simranjeet S Mirza Aashiq H AH Pociot Flemming F

Non-coding RNA 20181127 4

Understanding distinct cell-type specific gene expression in human pancreatic islets is important for developing islet regeneration strategies and therapies to improve β-cell function in type 1 diabetes (T1D). While numerous transcriptome-wide studies on human islet cell-types have focused on protein-coding genes, the non-coding repertoire, such as long non-coding RNA, including circular RNAs, remains mostly unexplored. Here, we explored transcriptional landscape of human α-, β-, and exocrine ce ...[more]

PMID: 30486482

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Project description:BackgroundCircular RNAs are non-coding RNA molecules with gene regulatory potential that have been associated with several human diseases. They are stable and present in the circulation, making them excellent candidates for biomarkers of disease. Despite their promise as biomarkers or future therapeutic targets, information on their expression and functionality in human pancreatic islets is a relatively unexplored subject.MethodsHere we aimed to produce an enriched circRNAome profile for human pancreatic islets by CircleSeq, and to explore the relationship between circRNA expression, diabetes status, genotype at T2D risk loci and measures of glycaemia (insulin secretory index; SI and HbA1c) in human islet preparations from healthy control donors and donors with type 2 diabetes using ANOVA or linear regression as appropriate. We also assessed the effect of elevated glucose, cytokine and lipid and hypoxia on circRNA expression in the human beta cell line EndoC-βH1.ResultsWe identified over 2600 circRNAs present in human islets. Of the five most abundant circRNAs in human islets, four (circCIRBP, circZKSCAN, circRPH3AL and circCAMSAP1) demonstrated marked associations with diabetes status. CircCIRBP demonstrated an association with insulin secretory index in isolated human islets and circCIRBP and circRPH3AL displayed altered expression with elevated fatty acid in treated EndoC-βH1 cells. CircCAMSAP1 was also noted to be associated with T2D status in human peripheral blood. No associations between circRNA expression and genotype at T2D risk loci were identified in our samples.ConclusionsOur data suggest that circRNAs are abundantly expressed in human islets, and that some are differentially regulated in the islets of donors with type 2 diabetes. Some islet circRNAs are also expressed in peripheral blood and the expression of one, circCAMSAP1, correlates with diabetes status. These findings highlight the potential of circRNAs as biomarkers for T2D.

Dataset Information

Cell Type-Selective Expression of Circular RNAs in Human Pancreatic Islets.

Publications

Cell Type-Selective Expression of Circular RNAs in Human Pancreatic Islets.

Similar Datasets

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