The hedgehog signaling pathway is a vital factor for embryonic development and stem cell maintenance. Dysregulation of its function results in tumor initiation and progression. The aim of this research was to establish a disease model of hedgehog-related tumorigenesis with Gorlin syndrome-derived induced pluripotent stem cells (GS-iPSCs). Induced neural progenitor cells from GS-iPSCs (GS-NPCs) show constitutive high GLI1 expression and higher sensitivity to smoothened (SMO) inhibition compared with wild-type induced neural progenitor cells (WT-NPCs). The differentiation process from iPSCs to NPCs may have similarity in gene expression to Hedgehog signal-related carcinogenesis. Therefore, GS-NPCs may be useful for screening compounds to find effective drugs to control Hedgehog signaling activity.

hedgehog 信号通路是胚胎发育和干细胞维持的重要因素。其功能失调导致肿瘤的发生和发展。本研究的目的是利用 Gorlin 综合征衍生的诱导多能干细胞 (GS-iPSC) 建立刺猬相关肿瘤发生的疾病模型。与野生型诱导神经祖细胞 (WT-NPC) 相比，来自 GS-iPSC (GS-NPC) 的诱导神经祖细胞显示出组成型高 GLI1 表达和对平滑 (SMO) 抑制的更高敏感性。从 iPSC 到 NPC 的分化过程可能在基因表达上与 Hedgehog 信号相关的致癌作用具有相似性。因此，GS-NPC 可用于筛选化合物以找到控制 Hedgehog 信号活性的有效药物。