Single-Cell RNA-Seq Analysis of Cells from Degenerating and Non-Degenerating Intervertebral Discs from the Same Individual Reveals New Biomarkers for Intervertebral Disc Degeneration

International Journal of Molecular Sciences

卷:23

Alain Sarabia Pacis¹  Jiannis Ragoussis²  Jean A. Ouellet³  Oded Rabau³  Hosni Cherif⁴  Lisbet Haglund⁴  Matthew Mannarino⁴ 

[1] Canadian Centre for Computational Genomics, McGill University Genome Center, 740 Dr. Penfield Avenue, Montreal, QC H3A 0G4, Canada;

[2] Department of Human Genetics, McGill University Genome Center, 740 Dr. Penfield Avenue, Montreal, QC H3A 0G4, Canada;

[3] McGill Scoliosis and Spine Group, Department of Surgery, The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC H3A 0G4, Canada;

[4] Orthopaedic Research Lab, Department of Surgery, The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC H3A 0G4, Canada;

关键词: single cell RNA sequencing;    intervertebral disc;    cartilage;    disc degeneration;    chondrocytes;    senescence;   

DOI  :  10.3390/ijms23073993

来源: DOAJ

【 摘 要 】

In this study, we used single-cell transcriptomic analysis to identify new specific biomarkers for nucleus pulposus (NP) and inner annulus fibrosis (iAF) cells, and to define cell populations within non-degenerating (nD) and degenerating (D) human intervertebral discs (IVD) of the same individual. Cluster analysis based on differential gene expression delineated 14 cell clusters. Gene expression profiles at single-cell resolution revealed the potential functional differences linked to degeneration, and among NP and iAF subpopulations. GO and KEGG analyses discovered molecular functions, biological processes, and transcription factors linked to cell type and degeneration state. We propose two lists of biomarkers, one as specific cell type, including C2orf40, MGP, MSMP, CD44, EIF1, LGALS1, RGCC, EPYC, HILPDA, ACAN, MT1F, CHI3L1, ID1, ID3 and TMED2. The second list proposes predictive IVD degeneration genes, including MT1G, SPP1, HMGA1, FN1, FBXO2, SPARC, VIM, CTGF, MGST1, TAF1D, CAPS, SPTSSB, S100A1, CHI3L2, PLA2G2A, TNRSF11B, FGFBP2, MGP, SLPI, DCN, MT-ND2, MTCYB, ADIRF, FRZB, CLEC3A, UPP1, S100A2, PRG4, COL2A1, SOD2 and MT2A. Protein and mRNA expression of MGST1, vimentin, SOD2 and SYF2 (p29) genes validated our scRNA-seq findings. Our data provide new insights into disc cells phenotypes and biomarkers of IVD degeneration that could improve diagnostic and therapeutic options.

【 授权许可】

Unknown