From the Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.
Department of Pediatrics, Oita University Faculty of Medicine, Yufu, Japan.
J Neuropathol Exp Neurol. 2021 Jan 20;80(2):129-136. doi: 10.1093/jnen/nlaa141.
Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1 and GLI3 are highly expressed in SHH-activated medulloblastoma, whereas GLI3 but not GLI1 is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.
胶质细胞瘤相关癌基因同源物 3（GLI3），其主要功能是抑制 GLI1，与髓母细胞瘤中的神经元分化有关。然而，尚不清楚哪些分子亚型显示出 GLI3 表达增加。通过免疫组织化学在 2 个独立队列中评估了 GLI3 水平，共包括 88 例，结果发现 WNT 和 SHH 激活的髓母细胞瘤中 GLI3 水平均较高。对批量 mRNA 表达数据和单细胞 RNA 测序研究的分析证实，SHH 激活的髓母细胞瘤中 GLI1 和 GLI3 表达水平较高，而 WNT 激活的髓母细胞瘤中仅 GLI3 而不是 GLI1 表达水平较高。免疫组织化学分析表明，SHH 激活的髓母细胞瘤中 GLI3 表达在神经元分化结节内，而 GLI1/2 表达在黏液样区。相比之下，在 WNT 激活的髓母细胞瘤中 GLI3 弥漫表达，而 GLI1 受到抑制。我们的数据表明，GLI3 可能是这些亚组中神经元分化和形态的主要调节因子。
