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

Area of Science:

• Biomedical Science
• Cell Biology
• Regenerative Medicine

Background:

• The human intervertebral disc (IVD) microenvironment and degeneration (IVDD) mechanisms are complex and poorly understood.
• Elucidating cellular heterogeneity is crucial for understanding IVDD pathogenesis.

Purpose of the Study:

• To characterize the cellular landscapes of nucleus pulposus (NP), annulus fibrosus (AF), and immunocytes in human IVD using scRNA-seq.
• To identify cellular changes and interactions during different stages of IVDD.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of human IVD tissues.
• Analysis of NP and AF subclusters and immunocyte populations.
• Investigation of cellular lineage trajectories and intercellular crosstalk.

Main Results:

• Identified six NP and seven AF subclusters with distinct functions and distributions across degeneration stages (Pfirrmann I-V).
• Discovered MCAM+, CD24+, and MKI67+ progenitor cells in AF and NP, respectively, with a lineage trajectory during IVDD.
• Observed a significant increase in monocyte/macrophage (Mφ) in degenerated IVDs, including Mφ-SPP1, which is specific to IVDD.

Conclusions:

• This study provides a comprehensive cellular atlas of human IVDD, revealing novel progenitor cells and immune cell dynamics.
• The findings elucidate key intercellular interactions and microenvironmental changes during IVDD.
• These insights offer potential therapeutic targets for mitigating IVDD progression.