Wnt signaling induces the myogenic specification of resident CD45+ adult stem cells during muscle regeneration
Wnt signaling induces the myogenic specification of resident CD45+ adult stem cells during muscle regeneration
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DOI：
10.1016/s0092-8674(03)00437-9
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发表时间：
2003-06-27
期刊：
影响因子：
64.5
通讯作者：
Rudnicki, MA
中科院分区：
文献类型：
--
作者：
Polesskaya, A;Seale, P;Rudnicki, MA
注入循环系统的CD45(+)干细胞参与肌肉再生的观察提出了肌肉中驻留的CD45(+)干细胞是否在再生过程中发挥生理作用的问题。我们发现从未受伤的肌肉中培养的CD45(+)细胞一致是非生肌性的。然而，从再生肌肉中纯化的CD45(+)细胞很容易产生确定的成肌细胞。损伤后肌肉中CD45(+)细胞数量迅速增加，并且大部分进入细胞周期。对参与胚胎肌发生的候选途径的研究表明，Wnt 信号传导足以诱导肌肉来源的 CD45(+) 干细胞的肌原性规范。此外，将Wnt拮抗剂sFRP2/3注射到再生肌肉中可显着降低CD45(+)干细胞增殖和肌源性规范。因此，我们的数据表明，驻留 CD45(+) 干细胞的动员是损伤后再生的重要因素，并强调 Wnt 通路作为退行性神经肌肉疾病的潜在治疗靶点。
The observation that CD45(+) stem cells injected into the circulation participate in muscle regeneration raised the question of whether CD45(+) stem cells resident in muscle play a physiological role during regeneration. We found that CD45(+) cells cultured from uninjured muscle were uniformly nonmyogenic. However, CD45(+) cells purified from regenerating muscle readily gave rise to determined myoblasts. The number of CD45(+) cells in muscle rapidly expanded following injury, and a high proportion entered the cell cycle. Investigation of candidate pathways involved in embryonic myogenesis revealed that Wnt signaling was sufficient to induce the myogenic specification of muscle-derived CD45(+) stem cells. Moreover, injection of the Wnt antagonists sFRP2/3 into regenerating muscle markedly reduced CD45(+) stem cell proliferation and myogenic specification. Our data therefore suggest that mobilization of resident CD45(+) stem cells is an important factor in regeneration after injury and highlight the Wnt pathway as a potential therapeutic target for degenerative neuromuscular disease.