Comprehensive sequencing profile and functional analysis of IsomiRs in human pancreatic islets and beta cells
Authors' conclusion
This study provides the first comprehensive isomiR profiling in human islets and beta cells, revealing their substantial contribution to miRNA regulation. IsomiR-411-5p-Ext5p(+1) emerges as a distinct key modulator of insulin secretion and granule dynamics in beta cells. These findings highlight isomiRs as potential biomarkers and therapeutic targets for diabetes, warranting further exploration of their roles in beta cell biology.
Study context
- Population
- Human pancreatic islets and beta cells from four beta cell sources
- Comparison
- Laser capture microdissected human islets (LCM-HI) vs collagenase-isolated human islets (CI-HI) vs Sorted beta cells vs EndoC-βH1
- Outcome
- isomiR expression profile (share of total miRNA reads)
Methodological detailssmall RNA-seq, cross-validation across datasets, functional validation by overexpression
- Small RNA-seq
- Cross-validation across datasets
- Functional validation by overexpression
Main finding
As reported in the abstract
- Beta cell-specific isomiR signature (sequences)
- 30
Further findings
Correlation of isomiR-411-5p-Ext5p(+1) with in vivo insulin secretion (LCM-HI)
- Inverse correlation with basal insulin secretion, partial R2=0.68
- P = 0.0009
- Inverse correlation with total insulin secretion, partial R2=0.54
- P = 0.005
Glucose-stimulated insulin secretion (GSIS) after isomiR-411-5p-Ext5p(+1) overexpression in EndoC-βH1 cells
- GSIS reduced by 51% (± 15.2%; mean ± SD); not with canonical counterpart
- P = 0.01
Transcriptomic analysis (EndoC-βH1 and CI-HI)
- Genes significantly downregulated by the isomiR but not canonical miRNA (FDR<0.05)
- 47
- Enriched pathway: Golgi vesicle biogenesis
- FDR=0.017
- Enriched pathway: trans-Golgi vesicle budding
- FDR=0.018
- TargetScan: seed sequence-dependent specificity, genes uniquely regulated by the isomiR
- 81 (p=1.1 × 10⁻⁹)
Original publication
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