Changes in the Oligodendrocyte Progenitor Cell Proteome with Ageing.
Changes in the Oligodendrocyte Progenitor Cell Proteome with Ageing.
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DOI：
10.1074/mcp.ra120.002102
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发表时间：
2020-08
期刊：
影响因子：
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通讯作者：
Franklin RJM
中科院分区：
文献类型：
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作者：
de la Fuente AG;Queiroz RML;Ghosh T;McMurran CE;Cubillos JF;Bergles DE;Fitzgerald DC;Jones CA;Lilley KS;Glover CP;Franklin RJM
少突胶质细胞祖细胞（OPC）介导的髓鞘再生随着年龄的增长而下降。我们使用定量 MS 蛋白质组学测定了新生、年轻和老年大鼠 OPC 的蛋白质组。我们发现随着衰老，髓磷脂蛋白会增加，OPC 中炎症、胆固醇生物合成和蛋白质稳态途径也会发生变化。这些数据为研究 OPC 与年龄相关的变化提供了资源，这些变化可能导致与年龄相关的少突胶质细胞生成减少。重点介绍新生儿、年轻和老年 OPC 的定量蛋白质组。新生儿和成人 OPC 之间 50% 的蛋白质组表达存在差异。随着年龄的增长，髓磷脂蛋白增加，胆固醇合成蛋白减少。老化的 OPC 中与其他神经退行性疾病相关的蛋白质会增加。中枢神经系统 (CNS) 脱髓鞘后，成体少突胶质细胞祖细胞 (OPC) 可以在称为髓鞘再生的再生过程中分化为新的形成髓磷脂的少突胶质细胞。尽管髓鞘再生在年轻人中非常有效，但其效率随着年龄的增长而逐渐下降。在这里，我们对从新生、年轻和老年雌性大鼠的大脑中新鲜分离的 OPC 进行了蛋白质组学分析。与成人相比，新生儿 OPC 中大约 50% 的蛋白质表达水平不同。髓磷脂相关蛋白以及与氧化磷酸化、炎症反应和肌动蛋白细胞骨架组织相关的蛋白的量随着年龄的增长而增加，而胆固醇生物合成、转录因子和细胞周期蛋白则减少。我们的实验提供了第一个老化 OPC 蛋白质组，揭示了不同年龄 OPC 的独特特征。这些研究为为什么髓鞘再生效率随着衰老而下降以及衰老的 OPC 在其他神经退行性疾病中的潜在作用提供了新的见解。
Oligodendrocyte progenitor cell (OPC)-mediated remyelination declines with ageing. We have determined the proteome of neonatal, young and aged rat OPCs using quantitative MS-proteomics. We identify increases in myelin proteins as well as changes in inflammation, cholesterol biosynthesis and protein homeostasis pathways in OPCs with ageing. These data provide a resource to study age-associated changes in OPCs that may contribute to the age-related decrease in oligodendrogliogenesis. Highlights Quantitative proteome of neonatal, young, and aged OPCs. 50% of the proteome is differentially expressed between neonatal and adult OPCs. Myelin proteins are increased, and cholesterol synthesis proteins decreased with age. Proteins associated with other neurodegenerative diseases are increased in aged OPCs. Following central nervous system (CNS) demyelination, adult oligodendrocyte progenitor cells (OPCs) can differentiate into new myelin-forming oligodendrocytes in a regenerative process called remyelination. Although remyelination is very efficient in young adults, its efficiency declines progressively with ageing. Here we performed proteomic analysis of OPCs freshly isolated from the brains of neonate, young and aged female rats. Approximately 50% of the proteins are expressed at different levels in OPCs from neonates compared with their adult counterparts. The amount of myelin-associated proteins, and proteins associated with oxidative phosphorylation, inflammatory responses and actin cytoskeletal organization increased with age, whereas cholesterol-biosynthesis, transcription factors and cell cycle proteins decreased. Our experiments provide the first ageing OPC proteome, revealing the distinct features of OPCs at different ages. These studies provide new insights into why remyelination efficiency declines with ageing and potential roles for aged OPCs in other neurodegenerative diseases.