ABSTRACT Human embryonic stem cells (hESC) are being exploited for potential use in cell transplantation due to their capacity for self-renewal and pluripotency. Dopamine (DA) neurons derived from hESC represent a promising source of cell replacement therapy for Parkinson’s disease (PD). While gene expression on the transcriptome level has been extensively studied, limited information is available for the proteome-level changes associated with DA neuron differentiation. Here we analyzed the proteome of differentiating DA neurons to search for the potential biomarkers to assess the efficiency of differentiation. Although the proteome profile of DA neurons did not exhibit significant changes, a number of cytoskeletal proteins including nuclear lamin, tropomyosin 1, and myosin light chain 1 were specifically up-regulated during differentiation. Expression analysis of the respective genes was also consistent with the proteome results. In addition, these differentially expressed proteins form protein interaction network with several PD-related proteins suggesting that they may play roles in PD pathogenesis as well as the maturation of DA neurons.

中文翻译：

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来自人类胚胎干细胞的分化多巴胺神经元的蛋白质组学分析

摘要人类胚胎干细胞 (hESC) 由于其自我更新和多能性的能力而被用于细胞移植的潜在用途。源自 hESC 的多巴胺 (DA) 神经元代表了帕金森病 (PD) 细胞替代疗法的有希望的来源。虽然转录组水平上的基因表达已被广泛研究，但与 DA 神经元分化相关的蛋白质组水平变化的可用信息有限。在这里，我们分析了分化 DA 神经元的蛋白质组，以寻找潜在的生物标志物来评估分化效率。虽然 DA 神经元的蛋白质组谱没有表现出显着变化，但许多细胞骨架蛋白（包括核纤层蛋白、原肌球蛋白 1 和肌球蛋白轻链 1）在分化过程中被特异性上调。各个基因的表达分析也与蛋白质组结果一致。此外，这些差异表达的蛋白质与多种 PD 相关蛋白质形成蛋白质相互作用网络，表明它们可能在 PD 发病机制以及 DA 神经元的成熟中发挥作用。