Microglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice?
Microglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice?
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DOI：
10.1084/jem.20202717
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发表时间：
2021-09-06
期刊：
影响因子：
--
通讯作者：
Colonna M
中科院分区：
文献类型：
--
作者：
Chen Y;Colonna M
对患者和小鼠模型中微观胶质细胞对阿尔茨海默病（AD）病理的反应进行的单细胞RNA测序（scRNA - seq）分析提供了重要见解，但也暴露出一些异质性和差异。在此，我们确定了一致的微观胶质细胞反应模式，并讨论了人类和小鼠之间的相似性和不一致性。
阿尔茨海默病的特征是淀粉样β肽的细胞外聚集、神经元内tau蛋白聚集以及神经元死亡。这种病理引发微观胶质细胞的激活。由于微观胶质细胞中表达的基因变异与AD风险相关，微观胶质细胞对病理的反应可能影响疾病进程。在小鼠AD模型中，单细胞RNA测序分析将这种反应描述为稳态微观胶质细胞逐渐转化为疾病相关微观胶质细胞（DAM）；在其他神经退行性疾病和神经炎症模型中也报道了其他反应性微观胶质细胞群体。我们回顾了所有这些微观胶质细胞的特征，重点强调了四种基本模式：疾病相关微观胶质细胞（DAM）、干扰素 - 微观胶质细胞、主要组织相容性复合体II类微观胶质细胞以及增殖性微观胶质细胞。我们提出，所有报道的微观胶质细胞群体要么只是其中一种，要么是多种的组合，这取决于所应用的聚类策略和疾病模型。我们进一步回顾了来自人类AD样本的单核RNA测序（snRNA - seq）数据，并讨论了人类和小鼠转录图谱之间存在相似性和差异的原因。最后，我们概述了阐明微观胶质细胞在AD发病机制中的影响的未来研究方向。
scRNA-seq analyses of microglial responses to AD pathology in patients and mouse models have provided fundamental insights but also exposed some heterogeneity and discrepancies. Here, we identify consistent microglial response patterns and discuss parallels and incongruities between humans and mice. Alzheimer’s disease (AD) is characterized by extracellular aggregates of amyloid β peptides, intraneuronal tau aggregates, and neuronal death. This pathology triggers activation of microglia. Because variants of genes expressed in microglia correlate with AD risk, microglial response to pathology plausibly impacts disease course. In mouse AD models, single-cell RNA sequencing (scRNA-seq) analyses delineated this response as progressive conversion of homeostatic microglia into disease-associated microglia (DAM); additional reactive microglial populations have been reported in other models of neurodegeneration and neuroinflammation. We review all of these microglial signatures, highlighting four fundamental patterns: DAM, IFN–microglia, MHC-II microglia, and proliferating microglia. We propose that all reported microglia populations are either just one or a combination, depending on the clustering strategy applied and the disease model. We further review single-nucleus RNA sequencing (snRNA-seq) data from human AD specimens and discuss reasons for parallels and discrepancies between human and mouse transcriptional profiles. Finally, we outline future directions for delineating the microglial impact in AD pathogenesis.
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耦合的增殖和凋亡维持成人大脑中小胶质细胞的快速离职。
影响因子：
8.8
作者：
Askew K;Li K;Olmos-Alonso A;Garcia-Moreno F;Liang Y;Richardson P;Tipton T;Chapman MA;Riecken K;Beccari S;Sierra A;Molnár Z;Cragg MS;Garaschuk O;Perry VH;Gomez-Nicola D
通讯作者：
Gomez-Nicola D
影响因子：
5.9
作者：
Douvaras P;Sun B;Wang M;Kruglikov I;Lallos G;Zimmer M;Terrenoire C;Zhang B;Gandy S;Schadt E;Freytes DO;Noggle S;Fossati V
通讯作者：
Fossati V
影响因子：
12.7
作者：
Boza-Serrano, Antonio;Ruiz, Rocio;Deierborg, Tomas
通讯作者：
Deierborg, Tomas
影响因子：
64.5
作者：
Gosselin D;Link VM;Romanoski CE;Fonseca GJ;Eichenfield DZ;Spann NJ;Stender JD;Chun HB;Garner H;Geissmann F;Glass CK
通讯作者：
Glass CK
影响因子：
16.2
作者：
Abud EM;Ramirez RN;Martinez ES;Healy LM;Nguyen CHH;Newman SA;Yeromin AV;Scarfone VM;Marsh SE;Fimbres C;Caraway CA;Fote GM;Madany AM;Agrawal A;Kayed R;Gylys KH;Cahalan MD;Cummings BJ;Antel JP;Mortazavi A;Carson MJ;Poon WW;Blurton-Jones M
通讯作者：
Blurton-Jones M