Comprehensive alpha, beta, and delta cell transcriptomics reveal an association of cellular aging with MHC class I upregulation

• Published in: Molecular metabolism (Germany) 2024-09, Vol.87, p.101990, Article 101990
• Main Authors: Staels, W., Berthault, C., Bourgeois, S., Laville, V., Lourenço, C., De Leu, N., Scharfmann, R.
• Format: Article
• Language: English
• Subjects: Aging - genetics; Aging - metabolism; Alpha cell; Animals; Animals, Newborn; Antigens, CD - genetics; Antigens, CD - metabolism; Beta cell; Cellular Senescence - genetics; Delta cell; Glucagon-Secreting Cells - metabolism; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; Insulin-Secreting Cells - metabolism; Islets of Langerhans - metabolism; Male; Maturation; MHC class I; Mice; Mice, Inbred C57BL; Pancreatic islet; Somatostatin-Secreting Cells - metabolism; Transcriptome; Up-Regulation
• ISSN: 2212-8778; 2212-8778
• DOI: 10.1016/j.molmet.2024.101990

This study aimed to evaluate the efficacy of a purification method developed for isolating alpha, beta, and delta cells from pancreatic islets of adult mice, extending its application to islets from newborn and aged mice. Furthermore, it sought to examine transcriptome dynamics in mouse pancreatic endocrine islet cells throughout postnatal development and to validate age-related alterations within these cell populations. We leveraged the high surface expression of CD71 on beta cells and CD24 on delta cells to FACS-purify alpha, beta, and delta cells from newborn (1-week-old), adult (12-week-old), and old (18-month-old) mice. Bulk RNA sequencing was conducted on these purified cell populations, and subsequent bioinformatic analyses included differential gene expression, overrepresentation, and intersection analysis. Alpha, beta, and delta cells from newborn and aged mice were successfully FACS-purified using the same method employed for adult mice. Our analysis of the age-related transcriptional changes in alpha, beta, and delta cell populations revealed a decrease in cell cycling and an increase in neuron-like features processes during the transition from newborn to adult mice. Progressing from adult to old mice, we identified an inflammatory gene signature related to aging (inflammaging) encompassing an increase in β-2 microglobulin and major histocompatibility complex (MHC) Class I expression. Our study demonstrates the effectiveness of our cell sorting technique in purifying endocrine subsets from mouse islets at different ages. We provide a valuable resource for better understanding endocrine pancreas aging and identified an inflammaging gene signature with increased β-2 microglobulin and MHC Class I expression as a common hallmark of old alpha, beta, and delta cells, with potential implications for immune response regulation and age-related diabetes. •CD71 expression on β-cells and CD24 on ∂-cells allows FACS purification of α-, β-, and ∂-cells from mouse pancreatic islets at different ages.•Age-related transcriptional changes in α-, β-, and ∂-cells revealed decreased cell cycling and increased neuronal features during the newborn-to-adult transition.•The adult-to-old transition is marked by an inflammatory signature (inflammaging) with increased β-2 microglobulin and MHC Class I expression.