Departments of Ophthalmology and Physiology, Neuroscience Program, University of California San Francisco, CA, USA.
Front Cell Neurosci. 2013 Mar 14;7:25. doi: 10.3389/fncel.2013.00025. eCollection 2013.
What roles do astrocytes play in human disease?This question remains unanswered for nearly every human neurological disorder. Yet, because of their abundance and complexity astrocytes can impact neurological function in many ways. The differentiation of human pluripotent stem cells (hPSCs) into neuronal and glial subtypes, including astrocytes, is becoming routine, thus their use as tools for modeling neurodevelopment and disease will provide one important approach to answer this question. When designing experiments, careful consideration must be given to choosing paradigms for differentiation, maturation, and functional analysis of these temporally asynchronous cellular populations in culture. In the case of astrocytes, they display heterogeneous characteristics depending upon species of origin, brain region, developmental stage, environmental factors, and disease states, all of which may render experimental results highly variable. In this review, challenges and future directions are discussed for using hPSC-derived astroglial progenitors and mature astrocytes for neurodevelopmental studies with a focus on exploring human astrocyte effects upon neuronal function. As new technologies emerge to measure the functions of astrocytes in vitro and in vivo, there is also a need for a standardized source of human astrocytes that are most relevant to the diseases of interest.
星形胶质细胞在人类疾病中扮演什么角色？对于几乎每一种人类神经紊乱疾病来说，这个问题仍然没有答案。然而，由于星形胶质细胞数量众多且结构复杂，它们可能会以多种方式影响神经功能。人类多能干细胞（hPSC）向神经元和神经胶质亚型（包括星形胶质细胞）的分化正变得常规化，因此，将其用作神经发育和疾病建模的工具将提供一种重要的方法来回答这个问题。在设计实验时，必须仔细考虑选择分化、成熟和功能分析这些在培养中具有时间异步细胞群体的范例。就星形胶质细胞而言，它们根据起源物种、脑区、发育阶段、环境因素和疾病状态表现出异质性特征，所有这些都可能使实验结果高度可变。在这篇综述中，讨论了使用 hPSC 衍生的星形胶质细胞祖细胞和成熟星形胶质细胞进行神经发育研究的挑战和未来方向，重点是探索人类星形胶质细胞对神经元功能的影响。随着新技术的出现，可以在体外和体内测量星形胶质细胞的功能，因此也需要一种最相关于感兴趣疾病的标准化人类星形胶质细胞来源。
