Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Department of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA.
Science. 2018 Apr 20;360(6386):331-335. doi: 10.1126/science.aao4750.
Gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) arise primarily in the midline of the central nervous system of young children, suggesting a cooperation between genetics and cellular context in tumorigenesis. Although the genetics of H3K27M-glioma are well characterized, their cellular architecture remains uncharted. We performed single-cell RNA sequencing in 3321 cells from six primary H3K27M-glioma and matched models. We found that H3K27M-glioma primarily contain cells that resemble oligodendrocyte precursor cells (OPC-like), whereas more differentiated malignant cells are a minority. OPC-like cells exhibit greater proliferation and tumor-propagating potential than their more differentiated counterparts and are at least in part sustained by signaling. Our study characterizes oncogenic and developmental programs in H3K27M-glioma at single-cell resolution and across genetic subclones, suggesting potential therapeutic targets in this disease.
H3K27M 突变型神经胶质瘤（H3K27M-glioma）主要发生于儿童中枢神经系统中线部位，提示其发生与遗传学和细胞环境之间存在协同作用。尽管 H3K27M 突变型神经胶质瘤的遗传学特征已得到很好的描述，但它们的细胞结构仍不清楚。我们对 6 例 H3K27M 突变型神经胶质瘤及其匹配模型中的 3321 个细胞进行了单细胞 RNA 测序。结果发现，H3K27M 突变型神经胶质瘤主要包含类似于少突胶质前体细胞（OPC-like）的细胞，而分化程度更高的恶性细胞则占少数。与分化程度更高的细胞相比，OPC-like 细胞具有更强的增殖和肿瘤传播能力，并且至少部分受到 Notch 信号的维持。本研究在单细胞分辨率和遗传亚克隆水平上对 H3K27M 突变型神经胶质瘤的致癌和发育程序进行了描述，为该疾病的潜在治疗靶点提供了线索。
