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. |
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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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