【原】神经干细胞和蛋白质组学

Neural Stem Cells (NSCs) and Proteomics.

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|核心内容：

神经干细胞(NSCs)可以自我更新，形成中枢神经系统的主要细胞类型。

神经干细胞的研究包括原代、中枢神经系统来源的细胞以及动物和人类胚胎干细胞(ESC)来源和诱导多能干细胞(IPSC)来源的研究。

神经干细胞为研究正常的神经发育、神经退行性变和神经系统疾病提供了一种手段，也是受损和疾病的中枢神经系统细胞修复的临床相关来源。

对神经干细胞的蛋白质组学研究有可能描绘出对神经干细胞生物学至关重要的分子和途径，以及神经干细胞参与神经修复的途径。

在这篇综述中，我们提供了NSC生物学的背景知识，包括获得NSC的方法和这些过程的注意事项。

然后，我们关注神经干细胞蛋白质组学研究的进展。这包括翻译后修饰(PTM)的分析；分析不同蛋白质组间(如分泌组)的方法；以及分析蛋白质组中的时间差异以阐明分化机制的方法。

我们还讨论了一些在神经干细胞研究中无疑会有用但尚未应用于该领域的方法。

虽然许多对神经干细胞的蛋白质组学研究在很大程度上编目了特定细胞状态的蛋白质组或翻译后修饰，但没有深入研究特定的功能，一些研究导致了对功能过程的理解或识别出无法通过其他手段识别的标记。

该领域仍然存在许多挑战，包括用于蛋白质组分析的神经干细胞的精确鉴定和标准化，以及如何将基础蛋白质组学研究转化为功能生物学。

下一层次的研究将需要跨学科的方法，将那些对蛋白质组学生物化学感兴趣的人的技能与那些对调节NSC功能感兴趣的人的技能结合起来。

原文摘要：

Neural stem cells (NSCs) can self-renew and give rise to the major cell types of the CNS. Studies of NSCs include the investigation of primary, CNS-derived cells as well as animal and human embryonic stem cell (ESC)-derived and induced pluripotent stem cell (iPSC)-derived sources. NSCs provide a means with which to study normal neural development, neurodegeneration, and neurological disease and are clinically relevant sources for cellular repair to the damaged and diseased CNS. Proteomics studies of NSCs have the potential to delineate molecules and pathways critical for NSC biology and the means by which NSCs can participate in neural repair. In this review, we provide a background to NSC biology, including the means to obtain them and the caveats to these processes. We then focus on advances in the proteomic interrogation of NSCs. This includes the analysis of posttranslational modifications (PTMs); approaches to analyzing different proteomic compartments, such the secretome; as well as approaches to analyzing temporal differences in the proteome to elucidate mechanisms of differentiation. We also discuss some of the methods that will undoubtedly be useful in the investigation of NSCs but which have not yet been applied to the field. While many proteomics studies of NSCs have largely catalogued the proteome or posttranslational modifications of specific cellular states, without delving into specific functions, some have led to understandings of functional processes or identified markers that could not have been identified via other means. Many challenges remain in the field, including the precise identification and standardization of NSCs used for proteomic analyses, as well as how to translate fundamental proteomics studies to functional biology. The next level of investigation will require interdisciplinary approaches, combining the skills of those interested in the biochemistry of proteomics with those interested in modulating NSC function.

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参考文献：https:///10.1074/mcp.O115.052704