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Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution

机译:小鼠和人类小胶质细胞在单细胞分辨率下的时空异质性

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摘要

Microglia have critical roles not only in neural development and homeostasis, but also in neurodegenerative and neuroinflammatory diseases of the central nervous system(1-4). These highly diverse and specialized functions may be executed by subsets of microglia that already exist in situ, or by specific subsets of microglia that develop from a homogeneous pool of cells on demand. However, little is known about the presence of spatially and temporally restricted subclasses of microglia in the central nervous system during development or disease. Here we combine massively parallel single-cell analysis, single-molecule fluorescence in situ hybridization, advanced immunohistochemistry and computational modelling to comprehensively characterize subclasses of microglia in multiple regions of the central nervous system during development and disease. Single-cell analysis of tissues of the central nervous system during homeostasis in mice revealed specific time- and region-dependent subtypes of microglia. Demyelinating and neurodegenerative diseases evoked context-dependent subtypes of microglia with distinct molecular hallmarks and diverse cellular kinetics. Corresponding clusters of microglia were also identified in healthy human brains, and the brains of patients with multiple sclerosis. Our data provide insights into the endogenous immune system of the central nervous system during development, homeostasis and disease, and may also provide new targets for the treatment of neurodegenerative and neuroinflammatory pathologies.
机译:小胶质细胞不仅在神经发育和体内稳态中起着关键作用,而且在中枢神经系统的神经退行性疾病和神经炎性疾病中也具有重要作用(1-4)。这些高度多样化和专门化的功能可以由已经就地存在的小胶质细胞的子集执行,也可以由按需从同质细胞池中发育的小胶质细胞的特定子集执行。然而,关于发育或疾病期间中枢神经系统中小胶质细胞在空间和时间上受限制的亚类的存在知之甚少。在这里,我们结合大规模并行单细胞分析,单分子荧光原位杂交,先进的免疫组织化学和计算模型,以全面表征发育和疾病期间中枢神经系统多个区域的小胶质细胞亚类。在小鼠体内稳态期间对中枢神经系统组织的单细胞分析显示了小胶质细胞的特定时间和区域依赖性亚型。脱髓鞘和神经退行性疾病引起了小胶质细胞的上下文相关亚型,具有不同的分子特征和不同的细胞动力学。在健康的人类大脑以及多发性硬化症患者的大脑中,也发现了相应的小胶质细胞簇。我们的数据提供了在发育,体内稳态和疾病过程中中枢神经系统内源性免疫系统的见解,也可能为神经退行性疾病和神经炎性疾病的治疗提供新的靶点。

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  • 来源
    《Nature》 |2019年第7744期|388-392|共5页
  • 作者单位

    Univ Freiburg, Inst Neuropathol, Med Fac, Freiburg, Germany;

    Univ Freiburg, Inst Neuropathol, Med Fac, Freiburg, Germany|Univ Freiburg, Berta Ottenstein Programme Clinician Scientists, Fac Med, Freiburg, Germany;

    Univ Freiburg, Inst Neuropathol, Med Fac, Freiburg, Germany;

    Charite Med Univ Berlin, Dept Neuropsychiat, Berlin, Germany|Charite Med Univ Berlin, Lab Mol Psychiat, Berlin, Germany;

    Univ Freiburg, Inst Neuropathol, Med Fac, Freiburg, Germany|Univ Freiburg, Fac Biol, Freiburg, Germany;

    Univ Freiburg, Clin Neurosurg, Fac Med, Freiburg, Germany;

    Univ Med Ctr Gottingen, Inst Neuropathol, Gottingen, Germany;

    Univ Med Ctr Gottingen, Inst Neuropathol, Gottingen, Germany;

    VIB Ctr Inflammat Res, Ghent, Belgium|Univ Ghent, Dept Biomed Mol Biol, Ghent, Belgium;

    Univ Freiburg, Med Fac, Dept Stereotact & Funct Neurosurg, Freiburg, Germany;

    Univ Freiburg, Med Fac, Dept Stereotact & Funct Neurosurg, Freiburg, Germany;

    Univ Hosp Essen, Dept Neurosurg, Essen, Germany;

    Univ Hosp Essen, Dept Neurosurg, Essen, Germany;

    Ruhr Univ Bochum, St Josef Hosp, Dept Neurol, Bochum, Germany;

    Charite Med Univ Berlin, Dept Neuropsychiat, Berlin, Germany|Charite Med Univ Berlin, Lab Mol Psychiat, Berlin, Germany|DZNE, Berlin, Germany|Univ Edinburgh, UK DRI, Edinburgh, Midlothian, Scotland;

    Univ Med Ctr Gottingen, Inst Neuropathol, Gottingen, Germany;

    Univ Freiburg, Inst Neuropathol, Med Fac, Freiburg, Germany|Univ Freiburg, Signalling Res Ctr BIOSS, Freiburg, Germany|Univ Freiburg, Signalling Res Ctr CIBSS, Freiburg, Germany|Univ Freiburg, Ctr NeuroModulat, Fac Med, Freiburg, Germany;

  • 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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  • 正文语种 eng
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