A Single-cell Transcriptomic Atlas of Human Intervertebral Disc

Using high-precision transcriptomics to systematically map the atlas of human intervertebral disc (IVD) at single-cell resolution. Consequently, we found remarkable cellular diversity in the human IVD and identified a set of signature markers to recognize the cell types spatially. Furthermore, we deciphered a biological classification of chondrocyte subclusters with distinct role in the ECM homeostasis.Notably, the critical clues were also discovered for progenitor cells with bi-lineage differentiation trajectories in the nucleus pulposus, which discriminatively marked by the ancestry molecules PDGFRA and PROCR and highly enriched PDGF network. Finally, we uncovered the potential vital factors maintaining the IVD homeostasis from the intercellular crosstalk based on the signaling network landscape of the IVD microenvironment. Overall design: Single-cell sequencing of 91,295 IVD cells from 3 nucleus pulposus, 2 cartilage endplate and 2 annulus fibrosus in IVD using the 10X genomics Kit.本研究依托高精度转录组学技术，以单细胞分辨率系统绘制了人类椎间盘（intervertebral disc, IVD）细胞图谱。据此，本研究发现人类椎间盘具有显著的细胞异质性，并鉴定出一组可用于空间识别细胞类型的特征性标志物。进一步解析了在细胞外基质（extracellular matrix, ECM）稳态中发挥独特功能的软骨细胞亚簇的生物学分类。值得注意的是，本研究还在髓核（nucleus pulposus）中发现了具有双谱系分化轨迹的祖细胞的关键线索：该类细胞以谱系标志物PDGFRA和PROCR进行特异性标记，且显著富集血小板衍生生长因子（platelet-derived growth factor, PDGF）信号网络。最后，基于椎间盘微环境的信号网络图谱，本研究从细胞间通讯层面揭示了维持椎间盘稳态的潜在关键调控因子。实验设计概述：本研究使用10X Genomics试剂盒，对取自3例髓核、2例软骨终板（cartilage endplate）及2例纤维环（annulus fibrosus）的91295个椎间盘细胞开展了单细胞测序。