Department of Genetics, Stanford University, Stanford, CA, USA.
Stanford Medical Scientist Training Program, Stanford University, Stanford, CA, USA.
Nature. 2019 Jul;571(7764):205-210. doi: 10.1038/s41586-019-1362-5. Epub 2019 Jul 3.
The mammalian brain contains neurogenic niches that comprise neural stem cells and other cell types. Neurogenic niches become less functional with age, but how they change during ageing remains unclear. Here we perform single-cell RNA sequencing of young and old neurogenic niches in mice. The analysis of 14,685 single-cell transcriptomes reveals a decrease in activated neural stem cells, changes in endothelial cells and microglia, and an infiltration of T cells in old neurogenic niches. T cells in old brains are clonally expanded and are generally distinct from those in old blood, which suggests that they may experience specific antigens. T cells in old brains also express interferon-γ, and the subset of neural stem cells that has a high interferon response shows decreased proliferation in vivo. We find that T cells can inhibit the proliferation of neural stem cells in co-cultures and in vivo, in part by secreting interferon-γ. Our study reveals an interaction between T cells and neural stem cells in old brains, opening potential avenues through which to counteract age-related decline in brain function.
哺乳动物大脑包含神经发生龛，其中包括神经干细胞和其他细胞类型。神经发生龛随着年龄的增长而功能下降，但它们在衰老过程中如何变化尚不清楚。在这里，我们对年轻和年老的小鼠神经发生龛进行了单细胞 RNA 测序。对 14685 个单细胞转录组的分析揭示了激活的神经干细胞减少、内皮细胞和小胶质细胞变化以及 T 细胞在老年神经发生龛中的浸润。老年大脑中的 T 细胞克隆扩增，通常与老年血液中的 T 细胞不同，这表明它们可能经历特定的抗原。老年大脑中的 T 细胞也表达干扰素-γ，具有高干扰素反应的神经干细胞亚群在体内的增殖减少。我们发现 T 细胞可以在共培养物和体内抑制神经干细胞的增殖，部分是通过分泌干扰素-γ。我们的研究揭示了老年大脑中 T 细胞和神经干细胞之间的相互作用，为对抗与年龄相关的大脑功能下降开辟了潜在途径。
