Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution.
Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution.
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DOI：
10.1016/j.celrep.2017.09.039
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发表时间：
2017-10-10
期刊：
影响因子：
8.8
通讯作者：
Tsai LH
中科院分区：
文献类型：
--
作者：
Mathys H;Adaikkan C;Gao F;Young JZ;Manet E;Hemberg M;De Jager PL;Ransohoff RM;Regev A;Tsai LH
小胶质细胞是大脑中的组织驻留巨噬细胞，是对几乎任何扰动做出反应的损伤传感器，包括神经退行性疾病，如阿尔茨海默病（AD）。在这里，使用单细胞RNA测序，我们确定了从具有AD样表型的严重神经变性小鼠模型和对照小鼠的海马中分离的1，600多个个体小胶质细胞的转录组，这些细胞在神经变性进展期间的多个时间点。在这个神经变性模型中，我们发现了两种分子上不同的反应性小胶质细胞表型，分别由共调节的I型和II型干扰素应答基因模块代表。此外，我们的工作确定了以前未观察到的小胶质细胞对神经变性的反应的异质性，发现了疾病阶段特异性小胶质细胞状态，揭示了小胶质细胞对神经变性的细胞重编程轨迹，并揭示了潜在的转录程序。Mathys等人使用单细胞RNA测序来确定神经变性进展期间小胶质细胞的表型异质性。他们鉴定了多种疾病阶段特异性细胞状态，包括两种分子上不同的反应性小胶质细胞表型，分别由共调节的I型和II型干扰素应答基因模块代表。
Microglia, the tissue-resident macrophages in the brain, are damage sensors that react to nearly any perturbation, including neurodegenerative diseases such as Alzheimer’s disease (AD). Here, using single-cell RNA sequencing, we determined the transcriptome of more than 1,600 individual microglia cells isolated from the hippocampus of a mouse model of severe neurodegeneration with AD-like phenotypes and of control mice at multiple time points during progression of neurodegeneration. In this neurodegeneration model, we discovered two molecularly distinct reactive microglia phenotypes that are typified by modules of co-regulated type I and type II interferon response genes, respectively. Furthermore, our work identified previously unobserved heterogeneity in the response of microglia to neurodegeneration, discovered disease stage-specific microglia cell states, revealed the trajectory of cellular reprogramming of microglia in response to neurodegeneration, and uncovered the underlying transcriptional programs. Mathys et al. use single-cell RNA sequencing to determine the phenotypic heterogeneity of microglia during the progression of neurodegeneration. They identify multiple disease stage-specific cell states, including two molecularly distinct reactive microglia phenotypes that are typified by modules of co-regulated type I and type II interferon response genes, respectively.
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