Single-cell transcriptomics of peripheral blood in the aging mouse

Area of Science:

• Immunology
• Gerontology
• Hematology

Background:

• Hematopoietic system changes serve as biomarkers for immunosenescence and aging.
• Understanding age-related alterations in peripheral blood is crucial for identifying health risks.

Purpose of the Study:

• To characterize age-associated changes in cell-type composition and transcriptional profiles of mouse peripheral blood.
• To identify specific molecular and cellular markers of aging in the hematopoietic system.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of 14,588 peripheral blood cells from mice.
• Analysis of cell clusters, transcriptional profiles, and gene expression patterns related to age.

Main Results:

• Identified 17 distinct cell clusters.
• Observed age-related upregulation of antigen processing/presentation and chemokine signaling pathways.
• Detected downregulation of ribosome pathway genes and increased expression of senescence markers (Cdkn1a, Cdkn2a) in older mice.
• Discovered a unique cluster of senescent, apoptosis-resistant T cells in old blood, marked by low Cd28 and high Bcl2/Cdkn2a expression.

Conclusions:

• Aging significantly alters peripheral blood cell composition and gene expression in mice.
• Specific pathways and cell types, like senescent T cells, are indicative of aging and immunosenescence.
• scRNA-seq provides a powerful tool for dissecting age-related hematopoietic changes.