Integrated transcriptomics contrasts fatty acid metabolism with hypoxia response in β-cell subpopulations associated with glycemic control

Mario A. Miranda, Juan F. Macias-Velasco, Heather Schmidt, Heather A. Lawson

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 languageEnglish
Article number156
JournalBMC genomics
Volume24
Issue number1
DOIs
StatePublished - Dec 2023

Keywords

  • Bulk RNAseq
  • Diabetes
  • Hyperglycemia
  • Insulin
  • Mouse model
  • Obesity
  • Single-cell RNAseq
  • β-cell heterogeneity

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