Single-cell transcriptomics reveals heterogeneity and intercellular crosstalk in human intervertebral disc degeneration.

The complexity of the human intervertebral disc (IVD) has hindered the elucidation of the microenvironment and mechanisms underlying IVD degeneration (IVDD). Here we determined the landscapes of nucleus pulposus (NP), annulus fibrosus (AF), and immunocytes in human IVD by scRNA-seq. Six NP subclusters and seven AF subclusters were identified, whose functional differences and distribution during different stages of degeneration (Pfirrmann I-V) were investigated. We found MCAM progenitor in AF, as well as CD24 progenitor and MKI67 progenitor in NP, forming a lineage trajectory from CD24/MKI67 progenitors to EffectorNP_⅓ during IVDD. There is a significant increase in monocyte/macrophage (Mφ) in degenerated IVDs (p = 0.044), with Mφ-SPP1 exclusively found in IVDD but not healthy IVDs. Further analyses of the intercellular crosstalk network revealed interactions between major subpopulations and changes in the microenvironment during IVDD. Our results elucidated the unique characteristics of IVDD, thereby shedding light on therapeutic strategies.