Abstract
Background: Understanding how heterogeneous β-cell function impacts diabetes is imperative for therapy development. Standard single-cell RNA sequencing analysis illuminates some factors driving heterogeneity, but new strategies are required to enhance information capture. Results: We integrate pancreatic islet single-cell and bulk RNA sequencing data to identify β-cell subpopulations based on gene expression and characterize genetic networks associated with β-cell function in obese SM/J mice. We identify β-cell subpopulations associated with basal insulin secretion, hypoxia response, cell polarity, and stress response. Network analysis associates fatty acid metabolism and basal insulin secretion with hyperglycemic-obesity, while expression of Pdyn and hypoxia response is associated with normoglycemic-obesity. Conclusions: By integrating single-cell and bulk islet transcriptomes, our study explores β-cell heterogeneity and identifies novel subpopulations and genetic pathways associated with β-cell function in obesity.
Original language | English |
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Article number | 156 |
Journal | BMC genomics |
Volume | 24 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2023 |
Keywords
- Bulk RNAseq
- Diabetes
- Hyperglycemia
- Insulin
- Mouse model
- Obesity
- Single-cell RNAseq
- β-cell heterogeneity