Inder Verma, Dinorah Friedmann-Morvinski, Eric Bushong, Mark Ellisman (2014) CIL:47053, Mus musculus castaneus. CIL. Dataset

Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor in humans. Here we show that gliomas can originate from differentiated cells in the central nervous system (CNS), including cortical neurons. Transduction by oncogenic lentiviral vectors of neural stem cells (NSCs), astrocytes, or even mature neurons in the brains of mice can give rise to malignant gliomas. All the tumors, irrespective of the site of lentiviral vector injection (the initiating population), shared common features of high expression of stem or progenitor markers and low expression of differentiation markers. Microarray analysis revealed that tumors of astrocytic and neuronal origin match the mesenchymal GBM subtype. We propose that most differentiated cells in the CNS upon defined genetic alterations undergo dedifferentiation to generate a NSC or progenitor state to initiate and maintain the tumor progression, as well as to give rise to the heterogeneous populations observed in malignant gliomas.

胶质母细胞瘤（GBM）是人类最常见的侵袭性恶性原发性脑肿瘤。本研究揭示了胶质瘤可能起源于中枢神经系统（CNS）中的分化细胞，包括皮层神经元。通过致癌性慢病毒载体对小鼠脑中的神经干细胞（NSCs）、星形胶质细胞，甚至成熟神经元的转导，可以引发恶性胶质瘤。所有肿瘤，无论慢病毒载体注射的部位（起始细胞群），均具有共同特征：干细胞或祖细胞标记物的高表达和分化标记物的低表达。微阵列分析显示，起源于星形胶质细胞和神经元的肿瘤与间质性GBM亚型相匹配。我们提出，在CNS中，大多数分化细胞在特定的基因变异作用下发生去分化，以生成神经干细胞或祖细胞状态，从而启动并维持肿瘤进展，并产生恶性胶质瘤中观察到的异质细胞群。