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解析诱导多能干细胞来源的神经元发育过程中的蛋白质组动态变化。

Deciphering the Proteome Dynamics during Development of Neurons Derived from Induced Pluripotent Stem Cells.

机构信息

Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands.

Netherlands Proteomics Center, Padualaan 8, 3584 CH Utrecht, The Netherlands.

出版信息

J Proteome Res. 2020 Jun 5;19(6):2391-2403. doi: 10.1021/acs.jproteome.0c00070. Epub 2020 May 15.

DOI:10.1021/acs.jproteome.0c00070
PMID:32357013
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7281779/
Abstract

Neuronal development is a complex multistep process that shapes neurons by progressing though several typical stages, including axon outgrowth, dendrite formation, and synaptogenesis. Knowledge of the mechanisms of neuronal development is mostly derived from the study of animal models. Advances in stem cell technology now enable us to generate neurons from human induced pluripotent stem cells (iPSCs). Here we provide a mass spectrometry-based quantitative proteomic signature of human iPSC-derived neurons, i.e., iPSC-derived induced glutamatergic neurons and iPSC-derived motor neurons, throughout neuronal differentiation. Tandem mass tag 10-plex labeling was carried out to perform proteomic profiling of cells at different time points. Our analysis reveals significant expression changes (FDR < 0.001) of several key proteins during the differentiation process, e.g., proteins involved in the Wnt and Notch signaling pathways. Overall, our data provide a rich resource of information on protein expression during human iPSC neuron differentiation.

摘要

神经元发育是一个复杂的多步骤过程,通过经历几个典型阶段来塑造神经元,包括轴突生长、树突形成和突触发生。神经元发育机制的知识主要来自于动物模型的研究。干细胞技术的进步使我们能够从人类诱导多能干细胞 (iPSC) 中产生神经元。在这里,我们提供了基于质谱的人类 iPSC 衍生神经元的定量蛋白质组学特征,即 iPSC 衍生的兴奋性谷氨酸神经元和 iPSC 衍生的运动神经元,贯穿神经元分化过程。串联质量标签 10 plex 标记用于在不同时间点对细胞进行蛋白质组学分析。我们的分析揭示了分化过程中几个关键蛋白的显著表达变化 (FDR < 0.001),例如参与 Wnt 和 Notch 信号通路的蛋白。总的来说,我们的数据提供了人类 iPSC 神经元分化过程中蛋白质表达的丰富信息资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b311/7281779/99fb15cb4107/pr0c00070_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b311/7281779/d15881055b4a/pr0c00070_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b311/7281779/808ca695d09e/pr0c00070_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b311/7281779/8c03cf901d75/pr0c00070_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b311/7281779/ec18381c3a78/pr0c00070_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b311/7281779/99fb15cb4107/pr0c00070_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b311/7281779/d15881055b4a/pr0c00070_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b311/7281779/808ca695d09e/pr0c00070_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b311/7281779/8c03cf901d75/pr0c00070_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b311/7281779/ec18381c3a78/pr0c00070_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b311/7281779/99fb15cb4107/pr0c00070_0005.jpg

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