Description:
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>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.</jats:p>
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<jats:title>Results</jats:title>
<jats:p>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 <jats:italic>Pdyn</jats:italic> and hypoxia response is associated with normoglycemic-obesity.</jats:p>
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<jats:title>Conclusions</jats:title>
<jats:p>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.</jats:p>
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