Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Harvard Stem Cell Institute, Cambridge, MA, USA.
Nat Neurosci. 2019 Oct;22(10):1696-1708. doi: 10.1038/s41593-019-0491-3. Epub 2019 Sep 24.
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.
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。