Spatially multicellular variability of intervertebral disc degeneration by comparative single-cell analysis

Area of Science:

• Biomedical Sciences
• Cell Biology
• Regenerative Medicine

Background:

• Intervertebral disc degeneration (IDD) is a significant cause of back pain.
• Cellular heterogeneity within intervertebral discs (IVDs) is known, but alterations during degeneration are not fully understood.

Purpose of the Study:

• To elucidate the cellular and molecular changes in goat IVD cells during degeneration.
• To identify key cell populations and regulatory networks involved in IDD.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was performed on cells from healthy and degenerative goat IVDs across four anatomic sites.
• Bioinformatic analysis was used to identify cell clusters, their frequencies, and molecular signatures.

Main Results:

• Identified distinct cell populations: EGLN3+ StressCs (stress resistance), TGFBR3+ HomCs (homeostasis), and GPRC5A+ RegCs (repair).
• Observed fluctuations in these cell cluster frequencies and signatures with IDD progression.
• Found altered chondrogenic differentiation in PROCR+ progenitor cells and stemness exhaustion in notochord cells during IDD.
• Characterized CAV1+ endothelial cells interacting with chondrocytes via signaling pathways in degenerative IVDs.

Conclusions:

• IDD involves significant shifts in IVD cellular composition and function.
• Specific cell populations and their molecular pathways are critically altered during IDD.
• This study provides a foundation for understanding IDD pathogenesis and developing targeted therapeutic strategies.