We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Regulation of endocrine cell alternative splicing revealed by single-cell RNA sequencing in type 2 diabetes pathogenesis.
- Authors
Wang, Jin; Wen, Shiyi; Chen, Minqi; Xie, Jiayi; Lou, Xinhua; Zhao, Haihan; Chen, Yanming; Zhao, Meng; Shi, Guojun
- Abstract
The prevalent RNA alternative splicing (AS) contributes to molecular diversity, which has been demonstrated in cellular function regulation and disease pathogenesis. However, the contribution of AS in pancreatic islets during diabetes progression remains unclear. Here, we reanalyze the full-length single-cell RNA sequencing data from the deposited database to investigate AS regulation across human pancreatic endocrine cell types in non-diabetic (ND) and type 2 diabetic (T2D) individuals. Our analysis demonstrates the significant association between transcriptomic AS profiles and cell-type-specificity, which could be applied to distinguish the clustering of major endocrine cell types. Moreover, AS profiles are enabled to clearly define the mature subset of β-cells in healthy controls, which is completely lost in T2D. Further analysis reveals that RNA-binding proteins (RBPs), heterogeneous nuclear ribonucleoproteins (hnRNPs) and FXR1 family proteins are predicted to induce the functional impairment of β-cells through regulating AS profiles. Finally, trajectory analysis of endocrine cells suggests the β-cell identity shift through dedifferentiation and transdifferentiation of β-cells during the progression of T2D. Together, our study provides a mechanism for regulating β-cell functions and suggests the significant contribution of AS program during diabetes pathogenesis. Alternative splicing profiles of human pancreatic islets at single-cell resolution define endocrine cell types and reveal the dysregulated splicing programs in β-cell maturation in type 2 diabetes pathogenesis.
- Subjects
ENDOCRINE cells; ALTERNATIVE RNA splicing; TYPE 2 diabetes; RNA splicing; RNA sequencing; CELLULAR control mechanisms; NUCLEOPROTEINS
- Publication
Communications Biology, 2024, Vol 7, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-024-06475-0