Spatiotemporal Characterization of Human Early Intervertebral Disc Formation at Single-Cell Resolution

Authors：Zhou, Taifeng; Chen, Yu; Liao, Zhiheng; Zhang, Long; Su, Deying; Li, Zhuling; Yang, Xiaoming; Ke, Xiaona; Liu, Hengyu; Chen, Yuyu; Weng, Ricong; Shen, Huimin; Xu, Caixia; Wan, Yong; Xu, Ren^*; Su, Peiqiang^*

Source：Advanced Science, 2023, 10(14).

DOI：10.1002/advs.202206296

• annulus fibrosus
• intervertebral disc formation
• notochord
• nucleus pulposus
• single-cell RNA sequencing

The intervertebral disc (IVD) acts as a fibrocartilaginous joint to anchor adjacent vertebrae. Although several studies have demonstrated the cellular heterogeneity of adult mature IVDs, a single-cell transcriptomic atlas mapping early IVD formation is still lacking. Here, the authors generate a spatiotemporal and single cell-based transcriptomic atlas of human IVD formation at the embryonic stage and a comparative mouse transcript landscape. They identify two novel human notochord (NC)/nucleus pulposus (NP) clusters, SRY-box transcription factor 10 (SOX10)(+) and cathepsin K (CTSK)(+), that are distributed in the early and late stages of IVD formation and they are validated by lineage tracing experiments in mice. Matrisome NC/NP clusters, T-box transcription factor T (TBXT)(+) and CTSK+, are responsible for the extracellular matrix homeostasis. The IVD atlas suggests that a subcluster of the vertebral chondrocyte subcluster might give rise to an inner annulus fibrosus of chondrogenic origin, while the fibroblastic outer annulus fibrosus preferentially expresseds transgelin and fibromodulin . Through analyzing intercellular crosstalk, the authors further find that notochordal secreted phosphoprotein 1 (SPP1) is a novel cue in the IVD microenvironment, and it is associated with IVD development and degeneration. In conclusion, the single-cell transcriptomic atlas will be leveraged to develop preventative and regenerative strategies for IVD degeneration.

• Institution
  厦门大学; 中山大学; 武汉大学; 1; 南方医科大学