Fibronectin regulates Wnt7a signaling and satellite cell expansion.
Fibronectin regulates Wnt7a signaling and satellite cell expansion.
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DOI：
10.1016/j.stem.2012.09.015
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发表时间：
2013-01-03
期刊：
影响因子：
23.9
通讯作者：
Rudnicki, A.
中科院分区：
文献类型：
--
作者：
Bentzinger, C. Florian;Wang, Yu Xin;von Maltzahn, Julia;Soleimani, Vahab D.;Yin, Hang;Rudnicki, Michael A.;Rudnicki, A.
细胞外基质（ECM）在干细胞龛内的影响仍然知之甚少。我们发现Syndecan-4（Sdc 4）和Frizzled-7（Fzd 7）在卫星细胞中形成共受体复合物，并且ECM糖蛋白纤连蛋白（FN）与Sdc 4的结合刺激Wnt 7a诱导卫星干细胞对称扩增的能力。新激活的卫星细胞动态重塑其生态位的瞬时高水平表达FN。敲除FN在前瞻性分离的卫星细胞严重损害了他们的能力，重新填充卫星细胞龛。相反，在体内过度表达FN与Wnt 7a显着刺激卫星干细胞在再生肌肉中的扩增。因此，激活的卫星细胞通过FN的自体表达重塑其生态位，FN提供反馈以通过Fzd 7/Sdc 4共受体复合物刺激Wnt 7a信号传导。因此，FN和Wnt 7a在再生肌发生期间一起调节卫星干细胞和卫星肌源性细胞的稳态水平。
The influence of the extracellular matrix (ECM) within the stem cell niche remains poorly understood. We found that Syndecan-4 (Sdc4) and Frizzled-7 (Fzd7) form a co-receptor complex in satellite cells and that binding of the ECM glycoprotein Fibronectin (FN) to Sdc4 stimulates the ability of Wnt7a to induce the symmetric expansion of satellite stem cells. Newly activated satellite cells dynamically remodel their niche by transient high-level expression of FN. Knockdown of FN in prospectively isolated satellite cells severely impaired their ability to repopulate the satellite cell niche. Conversely, in vivo over-expression of FN with Wnt7a dramatically stimulated the expansion of satellite stem cells in regenerating muscle. Therefore, activating satellite cells remodel their niche through autologous expression of FN that provides feedback to stimulate Wnt7a signaling through the Fzd7/Sdc4 co-receptor complex. Thus, FN and Wnt7a together regulate the homeostatic levels of satellite stem cells and satellite myogenic cells during regenerative myogenesis.
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