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首页> 外文期刊>Nature >Single-cell analysis reveals T cell infiltration in old neurogenic niches
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Single-cell analysis reveals T cell infiltration in old neurogenic niches

机译：单细胞分析揭示了旧神经源性壁T中的T细胞浸润

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摘要

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-gamma, 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-gamma. 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.
机译：哺乳动物的大脑含有神经源性壁ches，其中包括神经干细胞和其他细胞类型。神经源利基随着年龄的增长而变得功能减弱，但是它们在衰老过程中如何变化仍不清楚。在这里，我们对小鼠的年轻和古老神经源性壁ches进行单细胞RNA测序。对14,685个单细胞转录组的分析显示，活化的神经干细胞减少，内皮细胞和小胶质细胞发生变化，T细胞在旧的神经源壁ches中浸润。老脑中的T细胞克隆扩增，通常与老血中的T细胞不同，这表明它们可能会经历特定的抗原。老大脑中的T细胞也表达干扰素-γ，而具有高干扰素应答的神经干细胞亚群则显示出体内增殖减少。我们发现，T细胞可以在共培养和体内抑制神经干细胞的增殖，部分是通过分泌干扰素-γ来实现的。我们的研究揭示了旧大脑中T细胞与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提供了可能的途径。

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  • 来源
    《Nature》 |2019年第7764期|205-210|共6页
  • 作者

    Dulken Ben W.; Buckley Matthew T.; Negredo Paloma Navarro; Saligrama Naresha; Cayrol Romain; Leeman Dena S.; George Benson M.; Boutet Stephane C.; Hebestreit Katja; Pluvinage John V.; Wyss-Coray Tony; Weissman Irving L.; Vogel Hannes; Davis Mark M.; Brunet Anne;

  • 作者单位

    Stanford Univ, Dept Genet, Stanford, CA 94305 USA|Stanford Univ, Stanford Med Scientist Training Program, Stanford, CA 94305 USA|Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA;

    Stanford Univ, Dept Genet, Stanford, CA 94305 USA;

    Stanford Univ, Dept Genet, Stanford, CA 94305 USA;

    Stanford Univ, Dept Immunol & Microbiol, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA;

    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA;

    Stanford Univ, Dept Genet, Stanford, CA 94305 USA|Stanford Univ, Canc Biol Program, Stanford, CA 94305 USA|Genentech Inc, Immunol Discovery, San Francisco, CA USA;

    Stanford Univ, Stanford Med Scientist Training Program, Stanford, CA 94305 USA|Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA;

    Fluidigm Corp, San Francisco, CA USA|10x Genom, Pleasanton, CA USA;

    Stanford Univ, Dept Genet, Stanford, CA 94305 USA|Verge Gen, San Francisco, CA USA;

    Stanford Univ, Stanford Med Scientist Training Program, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA;

    Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Glenn Labs Biol Aging, Stanford, CA 94305 USA;

    Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA;

    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA;

    Stanford Univ, Dept Immunol & Microbiol, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA;

    Stanford Univ, Dept Genet, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Glenn Labs Biol Aging, Stanford, CA 94305 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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