The Characterization of a Subependymal Giant Astrocytoma-Like Cell Line from Murine Astrocyte with mTORC1 Hyperactivation.
The Characterization of a Subependymal Giant Astrocytoma-Like Cell Line from Murine Astrocyte with mTORC1 Hyperactivation.
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mTORC1过度激活小鼠星形细胞的室管膜下巨大星形细胞样细胞系的表征。
DOI：
10.3390/ijms22084116
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发表时间：
2021-04-16
影响因子：
5.6
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Tang X;Angst G;Haas M;Yang F;Wang C
多发性硬化症（TSC）是由TSC 1（hamartin）或TSC 2（tuberin）中的失活突变引起的遗传性疾病，TSC 1或TSC 2是雷帕霉素复合物1（mTORC 1）信号通路的机制靶点的关键负调节剂。TSC影响包括大脑在内的多个器官。神经系统表现为大脑皮质结节、室管膜下结节（SEN）和室管膜下巨细胞星形细胞瘤（SEGA）。SEGA可能导致TSC患者脑积水，mTORC 1抑制剂是目前推荐的SEGA治疗方法。然而，SEGA研究的一个主要限制是缺乏用于机制研究和开发新疗法的细胞系或动物模型。在这项研究中，我们从自发永生化的小鼠星形胶质细胞中产生TSC 1缺陷的神经细胞，试图模仿人类SEGA。TSC 1缺陷细胞表现出mTORC 1超活化和从星形胶质细胞向神经干/祖细胞表型转变的特征。雷帕霉素在体外有效地降低了这些TSC 1缺陷细胞的mTORC 1活性。在体内，TSC 1缺陷细胞可以形成SEGA样肿瘤，雷帕霉素治疗可降低肿瘤生长。总的来说，我们的研究产生了一种新的SEGA样细胞系，对于研究mTORC 1驱动的神经组织分子和病理学改变非常宝贵。这些SEGA样细胞也为开发SEGA TSC患者的新治疗策略提供了机会。
Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in TSC1 (hamartin) or TSC2 (tuberin), crucial negative regulators of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. TSC affects multiple organs including the brain. The neurologic manifestation is characterized by cortical tubers, subependymal nodules (SEN), and subependymal giant cell astrocytoma (SEGA) in brain. SEGAs may result in hydrocephalus in TSC patients and mTORC1 inhibitors are the current recommended therapy for SEGA. Nevertheless, a major limitation in the research for SEGA is the lack of cell lines or animal models for mechanistic investigations and development of novel therapy. In this study, we generated TSC1-deficient neural cells from spontaneously immortalized mouse astrocytes in an attempt to mimic human SEGA. The TSC1-deficient cells exhibit mTORC1 hyperactivation and characteristics of transition from astrocytes to neural stem/progenitor cell phenotypes. Rapamycin efficiently decreased mTORC1 activity of these TSC1-deficient cells in vitro. In vivo, TSC1-deficient cells could form SEGA-like tumors and Rapamycin treatment decreased tumor growth. Collectively, our study generates a novel SEGA-like cell line that is invaluable for studying mTORC1-driven molecular and pathological alterations in neurologic tissue. These SEGA-like cells also provide opportunities for the development of novel therapeutic strategy for TSC patients with SEGA.
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影响因子：
6.2
作者：
Pintacuda G;Martín JM;Eggan KC
通讯作者：
Eggan KC
影响因子：
158.5
作者：
Krueger, Darcy A.;Care, Marguerite M.;Franz, David Neal
通讯作者：
Franz, David Neal
DOI：
10.1016/j.pedhc.2006.05.004
发表时间：
2007-03-01
期刊：
Journal of pediatric health care : official publication of National Association of Pediatric Nurse Associates & Practitioners
影响因子：
--
作者：
Leung, Alexander K C;Robson, W Lane M
通讯作者：
Robson, W Lane M
影响因子：
2.6
作者：
Tomoto K;Fujimoto A;Inenaga C;Okanishi T;Imai S;Ogai M;Fukunaga A;Nakamura H;Sato K;Obana A;Masui T;Arai Y;Enoki H
通讯作者：
Enoki H
星形胶质细胞的创伤性划伤会触发钙内流，激活 JNK/c-Jun/AP-1 通路并开启 GFAP 表达
影响因子：
6.2
作者：
Gao, Kai;Wang, Chen Ran;Yu, Albert Cheung Hoi
通讯作者：
Yu, Albert Cheung Hoi