Discovery of a peripheral Myh11-expressing nucleus pulposus cell population demontrating therapeutic potential for disc degeneration

Abstract

Continual turnover of nucleus pulposus (NP) cellularity is critical for maintaining intervertebral disc (IVD) homeostasis; however, the presence and identity of potential progenitor cells within the NP remain unclear. This study identifies NP cells expressing myosin heavy chain 11 (Myh11+ NPCs) through single-cell transcriptomic analysis of human adolescent NP cells and spatial transcriptomic mapping of the murine juvenile IVD. Lineage tracing reveals that a limited population of peripheral Myh11+ NPCs emerges during embryogenesis and contributes persistently to NP maturation, homeostasis, and aging in mice. Myh11+ NPCs exhibit sphere-forming capacity and multipotent differentiation potential in vitro. Consistent with these findings, inducible ablation of Myh11+ NPCs using a diphtheria toxin subunit alpha gene (DTA) system result in IVD degeneration. Therapeutically, either Myh11-specific deletion of nerve growth factor receptor (Ngfr) or transplantation of Myh11+ NPCs into injured NP tissues mitigates pathological progression in a mouse model of IVD degeneration. In conclusion, these findings identify a potential marker that delineates the this NPCs population with progenitor cells characteristics in both mice and humans, thereby facilitating the development of targeted therapeutic strategies for spinal disorders focused on this cell population. The authors identify Myh11+ nucleus pulposus cells that maintain disc health throughout life. Their loss accelerates degeneration, while targeting or transplanting them protects, offering a promising regenerative strategy for spinal disorders.