Islet β-cells physiological difference study of old and young mice based on single-cell transcriptomics

Area of Science:

• Cellular and Molecular Biology
• Aging Research
• Endocrinology

Background:

• Cellular senescence is a hallmark of aging, characterized by reduced proliferation but preserved function.
• Pancreatic beta-cells, crucial for glucose homeostasis, also undergo aging, yet their specific senescence phenotype remains poorly understood.
• Investigating age-related changes in beta-cells is vital for understanding metabolic health decline.

Purpose of the Study:

• To characterize the physiological senescence of pancreatic beta-cells in aged mice.
• To identify gene expression and functional changes associated with beta-cell aging.
• To explore the role of transcription factors in pancreatic beta-cell senescence.

Main Methods:

• Single-cell RNA sequencing (10x Genomics) was performed on pancreatic beta-cells from young (2.5 months) and old (20 months) C57BL/6 mice.
• Biosynthesis analysis was used to identify beta-cells.
• Differential gene expression analysis was conducted to compare aged and young beta-cells.

Main Results:

• A total of 47 differentially expressed genes were identified in aged beta-cells (fold change >1.5, P < 0.05).
• 27 genes were upregulated and 20 were downregulated in old mice.
• Key genes involved in cellular senescence, including metallothioneins (Mt1, Mt2) and mitochondrial genes, were identified. Transcription factors Jund and Fos emerged as critical regulators.

Conclusions:

• Significant differences exist in the transcriptome of pancreatic beta-cells between young and old mice.
• Specific genes and transcription factors play crucial roles in the aging process of pancreatic beta-cells.
• These findings provide novel insights and resources for future research into pancreatic aging.