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<p>Elucidating the identity of enthesis-resident progenitors is critical for advancing regenerative strategies, particularly in the context of the long-standing question of how is fibrocartilage formed at tendon enthesis (bone-tendon interface) under mechanical loading. To address the question of cellular origins of entheseal fibrocartilage, we first employed spatial transcriptional and single cell sequencing to identify a novel population of <i>Tnn</i>⁺ progenitor cells and delineate their lineage trajectories across developmental stages. Subsequently, we used a diphtheria toxin mediated ablation model targeting these <i>Tnn</i>⁺ progenitors and demonstrated their functional importance, as ablation resulted in hypoplastic phenotypes characterized by impaired fibrocartilage maturation. Furthermore, comparative single-cell profiling between unloaded entheses and normal entheses revealed that tendon unloading significantly diminished both the abundance and chondrogenic potential of <i>Tnn</i>⁺ progenitors. Collectively, these findings resolve fundamental questions regarding enthesis morphogenesis and provide mechanistic insights into how mechanical loading orchestrates this critical developmental process.</p><p></p>

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Identification of a new population of Tnn+ progenitors to form tendon enthesis fibrocartilage

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月21日

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  • Tao Zhang,
  • Lin Zhang,
  • Ziyang Yuan,
  • Linfeng Wang,
  • Jianzhong Hu,
  • Thomas Skutella,
  • Hongbin Lu

摘要

Elucidating the identity of enthesis-resident progenitors is critical for advancing regenerative strategies, particularly in the context of the long-standing question of how is fibrocartilage formed at tendon enthesis (bone-tendon interface) under mechanical loading. To address the question of cellular origins of entheseal fibrocartilage, we first employed spatial transcriptional and single cell sequencing to identify a novel population of Tnn⁺ progenitor cells and delineate their lineage trajectories across developmental stages. Subsequently, we used a diphtheria toxin mediated ablation model targeting these Tnn⁺ progenitors and demonstrated their functional importance, as ablation resulted in hypoplastic phenotypes characterized by impaired fibrocartilage maturation. Furthermore, comparative single-cell profiling between unloaded entheses and normal entheses revealed that tendon unloading significantly diminished both the abundance and chondrogenic potential of Tnn⁺ progenitors. Collectively, these findings resolve fundamental questions regarding enthesis morphogenesis and provide mechanistic insights into how mechanical loading orchestrates this critical developmental process.