A latent Axin2+/Scx+ progenitor pool is the central organizer of tendon healing. A latent Axin2+/Scx+ progenitor pool is the central organizer of tendon healing

A tendon’s ordered extracellular matrix (ECM) is integral for transmitting force and highly prone to injury. Whether and how tendon cells, or tenocytes, embedded within this dense ECM mobilize and contribute to healing is unknown. Here, we identify a specialized Axin2+ tenocyte population in mouse and human tendons that remains latent in homeostasis yet serves as a major source of tendon progenitors during healing. We show that Axin2+ tenocytes readily expand in vitro and express stem cell markers. In vivo, Axin2+ cells are major functional contributors to repair: Axin2+ tenocytes de-differentiate, expand, and re-adopt a tenocyte fate post-injury. Specific loss of Wnt secretion in Axin2+ cells alters their stem cell identity and disrupts their activation upon injury, severely compromising healing. Our work highlights Axin2+ tenocytes as quiescent stem cells embedded in dense matrix, which are uniquely regulated in an autocrine manner and are central organizers of robust tendon healing. Overall design: Investigation of transcriptional differences in Axin2+ vs. Axin2- tendon cell populations

肌腱的有序细胞外基质（extracellular matrix, ECM）在力的传递中发挥不可或缺的作用，且极易发生损伤。目前尚不明确嵌入该致密细胞外基质中的肌腱细胞（或称腱细胞，tenocytes）是否会被动员并参与损伤修复，以及其具体的动员机制。本研究在小鼠和人类肌腱中鉴定出一类特殊的Axin2阳性腱细胞（Axin2+ tenocytes）群体：该群体在生理稳态下处于静息状态，却在损伤修复过程中作为肌腱祖细胞的主要来源。研究显示，Axin2阳性腱细胞可在体外高效增殖，并表达干细胞标志物。在体内环境中，Axin2阳性细胞是损伤修复的核心功能参与者：损伤发生后，Axin2阳性腱细胞会经历去分化、增殖过程，随后重新定向为腱细胞表型。若特异性敲除Axin2阳性细胞的Wnt分泌功能，会改变其干细胞特性，并阻断其在损伤后的激活，从而严重削弱损伤修复效果。本研究揭示，Axin2阳性腱细胞是嵌入致密基质中的静息干细胞，其通过自分泌途径受到独特调控，是高效肌腱修复的核心调控枢纽。实验整体设计：对比分析Axin2阳性与Axin2阴性肌腱细胞群体的转录组差异。