A global view of altered ligand-receptor interactions in bone marrow aging based on single-cell sequencing

Area of Science:

• Gerontology
• Hematology
• Cell Biology

Background:

• Altered cell-cell communication is a key feature of aging.
• The specific impact on bone marrow aging is not well understood.
• Bone marrow aging affects hematopoietic stem cells and immune function.

Purpose of the Study:

• To investigate changes in cell-cell communication within the aging bone marrow.
• To identify specific ligand-receptor interactions affected by aging.
• To explore potential therapeutic interventions for bone marrow aging.

Main Methods:

• Single-cell transcriptome sequencing of bone marrow cells from young and old mice.
• Bioinformatic analysis to identify differential ligand-receptor interactions.
• Validation using flow cytometry and quantitative real-time PCR.

Main Results:

• Identified 384,124 interactions, including 2575 ligand-receptor pairs across 16 cell types.
• Detected 5560 significantly different interactions between young and old bone marrow.
• Differential interactions were enriched for senescence-associated secretory phenotypes.
• Supplementing specific extracellular ligands reversed senescence signs in aged hematopoietic stem cells.

Conclusions:

• Developed an effective single-cell sequencing pipeline for detecting bone marrow cell-cell interactions.
• Discovered age-related changes in ligand-receptor signaling pathways in the bone marrow.
• Identified a potential therapeutic strategy targeting extracellular ligands to mitigate bone marrow aging.