刺猬通路驱动源自非肌源性内皮祖细胞的融合阴性横纹肌肉瘤的发生。
Hedgehog Pathway Drives Fusion-Negative Rhabdomyosarcoma Initiated From Non-myogenic Endothelial Progenitors.
机构信息
Department of Oncology, MS-352, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Department of Computational Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
出版信息
Cancer Cell. 2018 Jan 8;33(1):108-124.e5. doi: 10.1016/j.ccell.2017.12.001.
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.
横纹肌肉瘤（RMS）是一种儿科软组织肉瘤，在组织学上类似于胚胎骨骼肌肉。RMS 发生在全身，而仅仅是肌源性起源并不能解释在没有骨骼肌的部位发生的 RMS。我们之前描述了一种 RMS 模型，该模型激活了条件性组成性激活 Smoothened 突变体（SmoM2）与 aP2-Cre。通过遗传命运图谱，我们表明 SmoM2 在 Cre 表达的内皮祖细胞中的表达导致成肌细胞的转分化和 RMS。我们表明，头颈部的内皮细胞和骨骼肌来源于 Kdr 表达的祖细胞，而 hedgehog 通路的激活导致成肌特异性因子的异常表达，这可能是驱动 RMS 发生的潜在机制。这些发现表明，RMS 可以起源于非肌源性细胞的异常发育。
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