Rejuvenation of THY1+ nucleus pulposus-derived stem cells promotes intervertebral disc regeneration through FGF10-FGFR1-CREB pathway and mitochondrial fission

作者：Haoxin Zhai, Zexin Wang, Shaoyi Wang, Zhicheng Liu, Dawang Zhao, Yiming Zhang, Yiming Zhang, Kaiwen Liu, Xiangzhen Kong, Qunbo Meng, Hanwen Gu, Lin Chen, Yu Zhang, Yu Zhang, Lei Cheng · 发表于：Journal of Advanced Research · 年份：2026 · DOI：10.1016/j.jare.2026.03.008 · 被引用次数：1 · 研究领域：Spine and Intervertebral Disc Pathology、Mesenchymal stem cell research、Tendon Structure and Treatment

• THY1 + NPSCs are the main regenerative cell clusters based on GEO scRNA-seq data of human healthy and degenerated nucleus pulposus. • FGF10 is identified as rejuvenation factor to correlate with THY1 + NPSCs senescence. • FGF10/FGFR1 axis regulates phosphorylation of CREB and inhibit ARG2/DRP1 mediated mitochondria fission. • Transplantation of FGF10 modulated THY1 + NPSCs provides promising regenerative therapy for intervertebral disc degeneration. • Rejuvenation of THY1 + Nucleus Pulposus-derived Stem Cells Promotes Intervertebral Disc Regeneration through FGF10-FGFR1-CREB Pathway and Mitochondrial Fission. Intervertebral disc degeneration (IVDD), a major cause of low back pain, is primarily characterized by compromised regeneration ability of nucleus pulposus-derived stem cells (NPSCs) owing to their senescence. The role of NPSCs as major regenerative cells in IVDD is garnering attention. However, the drivers and mechanisms of NPSCs reactivation and regeneration are poorly understood, limiting the development of targeted therapies. The fibroblast growth factor (FGF) family has shown increasing promise in tissue regeneration; however, the key factors involved in IVDD remain unclear. To elucidate the regenerative driver of NPSCs and the underlying anti-senescence mechanism to provide a potential therapeutic strategy. Single cell RNA sequencing (scRNA-seq) and bulk RNA sequencing were performed to identify the key NPSCs clusters and regenerative drivers in IVDD. Clinical IV...