Identification of Potential Targets for EGFR-Regulated Nucleus Pulposus Degeneration Using Single-Cell RNA Sequencing...

Area of Science:

• Cell Biology
• Molecular Biology
• Biomedical Research

Background:

• Nucleus pulposus cell (NPC) degeneration drives intervertebral disc degeneration (IVDD).
• The molecular mechanisms and cellular heterogeneity of NPC degeneration are not fully understood.
• Epidermal growth factor receptor (EGFR) signaling is implicated in NPC differentiation and matrix production.

Purpose of the Study:

• To identify the critical downstream regulatory molecule of EGFR in NPC degeneration.
• To elucidate the role of EGFR signaling in the pathogenesis of IVDD.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) data analysis (GSE165722 dataset).
• Pseudotime analysis, Gene Set Enrichment Analysis (GSEA), and Weighted Gene Correlation Network Analysis (WGCNA).
• Machine learning algorithms (Lasso, XGBoost, Random Forest), ROC curve analysis, and validation in clinical specimens and animal models.

Main Results:

• Fib-NPCs were identified as a late-stage degenerative subpopulation with upregulated EGFR.
• JAK1 was identified as a downstream regulatory target of EGFR.
• EGFR inactivation in mice attenuated JAK1 upregulation in degenerated nucleus pulposus regions.

Conclusions:

• EGFR signaling contributes to NPC degeneration by regulating JAK1.
• The EGFR-JAK1 pathway represents a potential therapeutic target for delaying IVDD progression.