Spatiotemporal characterization of human early intervertebral disc formation at single-cell resolution

Intervertebral disc (IVD) performs as a fibrocartilaginous joint to anchor adjacent vertebrae (VB) and is essential for the mechanical stabilization of axial skeleton. Although several studies have demonstrated the cellular heterogeneity of adult mature IVD, a single-cell transcriptomic atlas mapping early IVD formation is still lacking. Here, we generated the first spatiotemporal and single-cell based transcriptomic atlas of human IVD formation at embryonic stage, as well as a comparative mouse transcript landscape. The notochord (NC)/nucleus pulposus (NP) cells, vertebral chondrocytes, and annulus fibrosus (AF) cells were characterized. Our single-cell transcriptomic atlas that resolves spatiotemporally regulated cellular heterogeneity underlying early IVD development will be leveraged to develop preventative and regenerative strategies for IVD degeneration. Overall design: Three embryonic mouse axial skeleton at E11.5-13.5 were cryosectioned to a thickness of 10 µm, followed by spatial transcriptome analysis via 10x Genomics Visium.