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

Autor: Miranda MA; Department of Genetics, Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8232, Saint Louis, MO, 63110, USA., Macias-Velasco JF; Department of Genetics, Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8232, Saint Louis, MO, 63110, USA., Schmidt H; Department of Genetics, Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8232, Saint Louis, MO, 63110, USA., Lawson HA; Department of Genetics, Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8232, Saint Louis, MO, 63110, USA. lawson@wustl.edu.
Jazyk: angličtina
Zdroj: BMC genomics [BMC Genomics] 2023 Mar 28; Vol. 24 (1), pp. 156. Date of Electronic Publication: 2023 Mar 28.
DOI: 10.1186/s12864-023-09232-5
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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