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成人大脑海马神经干细胞和胶质母细胞瘤干细胞中的钙通道

Calcium Channels in Adult Brain Neural Stem Cells and in Glioblastoma Stem Cells.

作者信息

Coronas Valérie, Terrié Elodie, Déliot Nadine, Arnault Patricia, Constantin Bruno

机构信息

Laboratoire STIM, Université de Poitiers-CNRS ERL 7003, Poitiers, France.

出版信息

Front Cell Neurosci. 2020 Nov 13;14:600018. doi: 10.3389/fncel.2020.600018. eCollection 2020.

Abstract

The brain of adult mammals, including humans, contains neural stem cells (NSCs) located within specific niches of which the ventricular-subventricular zone (V-SVZ) is the largest one. Under physiological conditions, NSCs proliferate, self-renew and produce new neurons and glial cells. Several recent studies established that oncogenic mutations in adult NSCs of the V-SVZ are responsible for the emergence of malignant primary brain tumors called glioblastoma. These aggressive tumors contain a small subpopulation of cells, the glioblastoma stem cells (GSCs), that are endowed with proliferative and self-renewal abilities like NSCs from which they may arise. GSCs are thus considered as the cells that initiate and sustain tumor growth and, because of their resistance to current treatments, provoke tumor relapse. A growing body of studies supports that Ca signaling controls a variety of processes in NSCs and GSCs. Ca is a ubiquitous second messenger whose fluctuations of its intracellular concentrations are handled by channels, pumps, exchangers, and Ca binding proteins. The concerted action of the Ca toolkit components encodes specific Ca signals with defined spatio-temporal characteristics that determine the cellular responses. In this review, after a general overview of the adult brain NSCs and GSCs, we focus on the multiple roles of the Ca toolkit in NSCs and discuss how GSCs hijack these mechanisms to promote tumor growth. Extensive knowledge of the role of the Ca toolkit in the management of essential functions in healthy and pathological stem cells of the adult brain should help to identify promising targets for clinical applications.

摘要

包括人类在内的成年哺乳动物的大脑含有位于特定微环境中的神经干细胞(NSCs),其中脑室下室管膜区(V-SVZ)是最大的微环境。在生理条件下,神经干细胞增殖、自我更新并产生新的神经元和神经胶质细胞。最近的几项研究表明,V-SVZ成年神经干细胞中的致癌突变是导致称为胶质母细胞瘤的恶性原发性脑肿瘤出现的原因。这些侵袭性肿瘤含有一小部分细胞,即胶质母细胞瘤干细胞(GSCs),它们具有与可能产生它们的神经干细胞相似的增殖和自我更新能力。因此,胶质母细胞瘤干细胞被认为是启动和维持肿瘤生长的细胞,并且由于它们对当前治疗的抗性,会导致肿瘤复发。越来越多的研究支持钙信号传导控制神经干细胞和胶质母细胞瘤干细胞中的多种过程。钙是一种普遍存在的第二信使,其细胞内浓度的波动由通道、泵、交换器和钙结合蛋白处理。钙信号传导工具组件的协同作用编码具有确定的时空特征的特定钙信号,这些信号决定细胞反应。在这篇综述中,在对成年脑内神经干细胞和胶质母细胞瘤干细胞进行总体概述之后,我们将重点关注钙信号传导工具在神经干细胞中的多种作用,并讨论胶质母细胞瘤干细胞如何利用这些机制促进肿瘤生长。深入了解钙信号传导工具在成年脑健康和病理干细胞基本功能管理中的作用,应该有助于确定有前景的临床应用靶点。

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