单细胞转录组谱分析衰老小鼠大脑。

Single-cell transcriptomic profiling of the aging mouse brain.

机构信息

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.

Harvard Stem Cell Institute, Cambridge, MA, USA.

出版信息

Nat Neurosci. 2019 Oct;22(10):1696-1708. doi: 10.1038/s41593-019-0491-3. Epub 2019 Sep 24.

Abstract

The mammalian brain is complex, with multiple cell types performing a variety of diverse functions, but exactly how each cell type is affected in aging remains largely unknown. Here we performed a single-cell transcriptomic analysis of young and old mouse brains. We provide comprehensive datasets of aging-related genes, pathways and ligand-receptor interactions in nearly all brain cell types. Our analysis identified gene signatures that vary in a coordinated manner across cell types and gene sets that are regulated in a cell-type specific manner, even at times in opposite directions. These data reveal that aging, rather than inducing a universal program, drives a distinct transcriptional course in each cell population, and they highlight key molecular processes, including ribosome biogenesis, underlying brain aging. Overall, these large-scale datasets (accessible online at https://portals.broadinstitute.org/single_cell/study/aging-mouse-brain ) provide a resource for the neuroscience community that will facilitate additional discoveries directed towards understanding and modifying the aging process.

摘要

哺乳动物的大脑非常复杂,其中有多种细胞类型发挥着不同的功能,但大脑中每种细胞类型是如何受到衰老影响的,目前仍知之甚少。在此,我们对年轻和年老小鼠的大脑进行了单细胞转录组分析。我们提供了近乎所有脑细胞类型中与衰老相关的基因、途径和配体-受体相互作用的综合数据集。我们的分析确定了细胞类型间协调变化的基因特征,以及以细胞类型特异性方式调控的基因集,甚至有时是相反的方向。这些数据表明,衰老不是诱导普遍程序,而是在每个细胞群体中驱动独特的转录过程,它们突出了关键的分子过程,包括核糖体生物发生,这些过程是大脑衰老的基础。总的来说,这些大规模数据集(可在线在 https://portals.broadinstitute.org/single_cell/study/aging-mouse-brain 获得)为神经科学界提供了一个资源,将有助于进一步发现理解和改变衰老过程的方向。

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