Neurog2和Sox4诱导细胞重编程技术在胶质母细胞瘤上的应用及机制研究

胶质母细胞瘤（GBM）是神经系统最常见的恶性肿瘤，尽管近年来GBM在以手术治疗为主的综合治疗上取得了很大进步，但GBM的预后依然极差。科学家普遍认同的观点是GBM细胞是分化过程被阻断了的细胞。因此，促进GBM细胞分化为终末的不具备分裂能力的细胞，在理论上能够清除GBM细胞。申请者前期研究发现Neurog2和Sox4可重编程GBM细胞株U251为神经元样细胞，并阻断细胞增殖。因此，本课题旨在进一步深入研究Neurog2和Sox4对GBM细胞的体内重编程效果及其分子机制：（一）通过GBM裸鼠模型明确Neurog2和Sox4介导的细胞重编程对GBM的干扰效果；（二）通过RNAseq技术和ChIPseq技术获得Neurog2和Sox4作用GBM细胞后转录组数据和转录因子靶点基因信息，阐明该细胞重编程的潜在分子生物学机制；为GBM基因治疗提供科学基础。

Glioblastoma (GBM) is the most common malignant tumors in the central nervous system. Despite major advances in multimodal therapy, the survival rate for patients with GBM is still extremely poor. Scientists generally agree that GBM cells are cells whose differentiation process has been blocked. Therefore, promoting the differentiation of GBM cells into terminal cells without the ability to divide can theoretically eliminate GBM cells. We previously showed that glioblastoma cells (U251) can be efficiently reprogrammed by Neurog2 and Sox4 into terminally differentiated and non-proliferating neuron-like cells. Thus, we will further study the reprogramming effects of Neurog2 and Sox4 on GBM cells in vivo and underlying mechanism. The GBM nude mouse model was used to determine the feasibility of Neurog2 and Sox4 to reprogram GBM cells into neuron-like cells to treat GBM. To clarify potential molecular biological mechanism of the cell reprogramming, RNAseq and ChIPseq technology are used to obtain the transcriptome data and the direct target gene information of Neurog2 and Sox4 in GBM cells. Providing a scientific basis for GBM gene therapy.