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

IF 18.1 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2026-08-08 DOI:10.1038/s41467-026-76515-2

Long Zhang, Yu Chen, Xueqing Shi, Taifeng Zhou, Jie Han, Lin Meng, Na Li, Matthew B. Greenblatt, Zemin Ling, Peiqiang Su, Fuxin Wei, Ren Xu

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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.

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外周表达myh11的髓核细胞群的发现证明了椎间盘退变的治疗潜力

髓核（NP）细胞的持续更新是维持椎间盘（IVD）稳态的关键；然而，NP中潜在祖细胞的存在和身份仍不清楚。本研究通过对人类青少年NP细胞的单细胞转录组学分析和小鼠幼年期IVD的空间转录组学定位，鉴定了表达Myh11+ NPCs的NP细胞。谱系追踪显示，有限的外周Myh11+ npc群体在胚胎发生过程中出现，并持续参与小鼠NP成熟、体内平衡和衰老。Myh11+ npc在体外表现出球形形成能力和多能分化潜能。与这些发现一致，使用白喉毒素亚单位α基因（DTA）系统诱导消融Myh11+ npc导致IVD变性。在治疗上，Myh11特异性缺失神经生长因子受体（Ngfr）或Myh11+ NPCs移植到受损NP组织中可以减轻小鼠IVD退行性变模型的病理进展。总之，这些发现确定了一个潜在的标记物，该标记物描述了小鼠和人类中具有祖细胞特征的NPCs群体，从而促进了针对该细胞群体的脊柱疾病靶向治疗策略的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.