Cell autonomous TGFβ signaling is essential for stem/progenitor cell recruitment into degenerative tendons.
Cell autonomous TGFβ signaling is essential for stem/progenitor cell recruitment into degenerative tendons.
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DOI：
10.1016/j.stemcr.2021.10.018
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发表时间：
2021-12-14
影响因子：
5.9
通讯作者：
Schweitzer R
中科院分区：
文献类型：
--
作者：
Tan GK;Pryce BA;Stabio A;Keene DR;Tufa SF;Schweitzer R
了解受损肌腱中的细胞募集对于改善再生疗法至关重要。我们最近报道，定向破坏肌腱细胞谱系中的转化生长因子β (TGFβ) II 型受体 (Tgfbr2ScxCre) 导致出生后肌腱细胞去分化和肌腱退化。在这里，我们扩展了分析并确定了干细胞/祖细胞直接招募到退行性突变肌腱中。 Cre介导的谱系追踪表明，这些细胞并非源自肌腱鞘组织或表达Scleraxis的谱系，并且它们仅在进入突变肌腱时才开启肌腱标记物。通过免疫组织化学和诱导基因删除，我们进一步发现招募的细胞源自表达 Sox9 的谱系，并且它们的招募依赖于细胞自主的 TGFβ 信号传导。因此，本研究中鉴定的细胞与之前关于细胞募集到受伤肌腱中的报道不同，并表明 TGFβ 信号在细胞募集中发挥着关键作用，从而提供了可能支持肌腱修复改善的见解。 TGFβ信号传导的靶向缺失导致小鼠肌腱的退行性变化 干/祖细胞被招募到退行性突变体肌腱中 招募的细胞与迄今为止报道的肌腱损伤中的细胞不同 募集依赖于招募细胞中的细胞自主 TGFβ 信号传导 在本文中，Schweitzer 及其同事确定了新的干细胞/祖细胞群被招募到退行性突变体小鼠肌腱中，并证明它们的募集依赖于细胞自主 TGFβ 信号传导。这提供了直接检查肌腱干/祖细胞的起源及其激活机制的机会，这对于改善肌腱修复至关重要。
Understanding cell recruitment in damaged tendons is critical for improvements in regenerative therapy. We recently reported that targeted disruption of transforming growth factor beta (TGFβ) type II receptor in the tendon cell lineage (Tgfbr2ScxCre) resulted in resident tenocyte dedifferentiation and tendon deterioration in postnatal stages. Here we extend the analysis and identify direct recruitment of stem/progenitor cells into the degenerative mutant tendons. Cre-mediated lineage tracing indicates that these cells are not derived from tendon-ensheathing tissues or from a Scleraxis-expressing lineage, and they turned on tendon markers only upon entering the mutant tendons. Through immunohistochemistry and inducible gene deletion, we further find that the recruited cells originated from a Sox9-expressing lineage and their recruitment was dependent on cell autonomous TGFβ signaling. The cells identified in this study thus differ from previous reports of cell recruitment into injured tendons and suggest a critical role for TGFβ signaling in cell recruitment, providing insights that may support improvements in tendon repair. Targeted deletion of TGFβ signaling led to degenerative changes in mouse tendons Stem/progenitor cells were recruited into the degenerative mutant tendons The recruited cells are different from the ones so far reported in tendon injury Recruitment was dependent on cell autonomous TGFβ signaling in the recruited cells In this article, Schweitzer and colleagues identify the recruitment of a new population of stem/progenitors into degenerative mutant mouse tendons and demonstrate that their recruitment was dependent on cell autonomous TGFβ signaling. This provides an opportunity to directly examine the origin of tendon stem/progenitor cells and the mechanisms of their activation, which is critical for improvement in tendon repair.
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DOI：
10.1002/stem.2846
发表时间：
2018-09
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Cathery W;Faulkner A;Maselli D;Madeddu P
通讯作者：
Madeddu P
影响因子：
4.6
作者：
Hameyer, Dorothe;Loonstra, Ate;Bockamp, Ernesto
通讯作者：
Bockamp, Ernesto
影响因子：
2.8
作者：
Dahlgren, LA;Mohammed, HO;Nixon, AJ
通讯作者：
Nixon, AJ
影响因子：
10.5
作者：
Akiyama, H;Chaboissier, MC;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
82.9
作者：
Bi, Yanming;Ehirchiou, Driss;Young, Marian F.
通讯作者：
Young, Marian F.