Rhabdomyosarcoma (RMS) is a pediatric soft tissue sarcoma that histologically resembles embryonic skeletal muscle. RMS occurs throughout the body and an exclusively myogenic origin does not account for RMS occurring in sites devoid of skeletal muscle. We previously described an RMS model activating a conditional constitutively active Smoothened mutant (SmoM2) with aP2-Cre. Using genetic fate mapping, we show SmoM2 expression in Cre-expressing endothelial progenitors results in myogenic transdifferentiation and RMS. We show that endothelium and skeletal muscle within the head and neck arise from Kdr-expressing progenitors, and that hedgehog pathway activation results in aberrant expression of myogenic specification factors as a potential mechanism driving RMS genesis. These findings suggest that RMS can originate from aberrant development of non-myogenic cells.

中文翻译：

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刺猬通路驱动由非肌源性内皮祖细胞引发的融合阴性横纹肌肉瘤。

横纹肌肉瘤（RMS）是一种组织学上类似于胚胎骨骼肌的小儿软组织肉瘤。RMS发生在整个身体中，并且仅由肌源性引起的原因不能解释RMS发生在没有骨骼肌的部位。我们先前描述了一个RMS模型，该模型激活带有aP2-Cre的条件性组成型活性平滑化突变体（SmoM2）。使用遗传命运图谱，我们显示在Cre表达的内皮祖细胞中SmoM2表达导致肌源性转分化和RMS。我们显示头颈部的内皮细胞和骨骼肌是由表达Kdr的祖细胞产生的，并且刺猬途径的激活导致肌原性规格因子的异常表达，这是驱动RMS发生的潜在机制。