Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.
Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.
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神经胶质区域身份的重大转变是人脑衰老的转录标志。
DOI：
10.1016/j.celrep.2016.12.011
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发表时间：
2017-01-10
期刊：
影响因子：
8.8
通讯作者：
Ule J
中科院分区：
文献类型：
--
作者：
Soreq L;UK Brain Expression Consortium;North American Brain Expression Consortium;Rose J;Soreq E;Hardy J;Trabzuni D;Cookson MR;Smith C;Ryten M;Patani R;Ule J
基因表达研究表明，人类大脑的衰老是由分子事件的复杂相互作用决定的，尽管其区域和细胞类型特异性后果仍然知之甚少。在这里，我们广泛地描述了年龄从16岁到106岁的480个人的10个人脑区域中年龄改变的基因表达变化。我们发现，星形胶质细胞和少突胶质细胞特异性基因，但不是神经元特异性基因，改变其区域表达模式老化后，特别是在海马和黑质，而小胶质细胞和内皮细胞特异性基因的表达增加，在所有的大脑区域。与这些变化一致，高分辨率免疫组织化学显示，在老化的大脑皮层中，少突胶质细胞和神经元亚群的数量减少。最后，神经胶质特异性基因比神经元特异性基因更精确地预测年龄，从而突出了对衰老和老年疾病中神经元-神经胶质相互作用的更深入的机制理解的必要性。了解细胞类型特异性变化在人脑衰老中的作用胶质细胞特异性基因在衰老过程中改变其区域表达模式少突胶质细胞和神经元亚群在衰老新皮质中减少小胶质细胞特异性基因在衰老过程中整体增加其表达人脑衰老是由区域和细胞类型特异性分子事件的复杂相互作用决定的。Soreq等人发现神经胶质基因改变其区域表达模式，而小胶质细胞特异性基因在衰老时整体增加其表达。此外，免疫组织化学显示，在老化的新皮质少突胶质细胞和神经元亚群的数量减少。
Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases. Understanding the role of cell-type-specific changes in human brain aging Glial-specific genes shift their regional expression patterns during aging Oligodendrocytes and neuronal subpopulations are decreased in the aging neocortex Microglia-specific genes globally increase their expression during aging Human brain aging is determined by a complex interplay of regional and cell-type-specific molecular events. Soreq et al. find that glial genes shift their regional expression patterns, while microglia-specific genes globally increase their expression upon aging. Moreover, immunohistochemistry reveals decreased numbers of oligodendrocytes and neuronal subpopulations in the aging neocortex.