Multi-modal Single-Cell Analysis Reveals Brain Immune Landscape Plasticity during Aging and Gut Microbiota Dysbiosis.
Multi-modal Single-Cell Analysis Reveals Brain Immune Landscape Plasticity during Aging and Gut Microbiota Dysbiosis.
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DOI：
10.1016/j.celrep.2020.108438
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发表时间：
2020-12-01
期刊：
影响因子：
8.8
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Golomb SM;Guldner IH;Zhao A;Wang Q;Palakurthi B;Aleksandrovic EA;Lopez JA;Lee SW;Yang K;Zhang S
脑免疫细胞的表型和功能可塑性有助于脑组织的稳态和疾病。免疫细胞的可塑性受到组织微环境和系统因素的深刻影响。重塑大脑免疫细胞可塑性和稳态的衰老和肠道微生物群失调尚未完全阐明。使用转录组和表位的细胞索引测序（CITE-seq），我们分析了大脑免疫景观的组成和转录变化，以应对衰老和肠道生态失调。典型的表面标记物定义的免疫细胞类型和它们的转录组之间的不一致性表明免疫细胞之间的转录可塑性。Ly 6C+单核细胞在老年大脑中占主导地位的促炎特征，而先天淋巴样细胞（ILC）向ILC 2样特征转变。衰老增加了表达T记忆干细胞（Tscm）特征的ILC样细胞，该特征通过抗生素诱导的肠道生态失调而减少。由于衰老和肠道生态失调引起的全身变化增加了神经炎症的倾向，为年龄相关神经系统疾病中的肠道生态失调提供了见解。Golomb等人通过对有和无抗生素诱导的肠道生态失调的年轻和老年雌性小鼠脑中的免疫细胞进行测序，对转录组和表位进行细胞索引。单细胞分析揭示了老年人大脑中单核细胞和先天淋巴细胞的转录可塑性。
Phenotypic and functional plasticity of brain immune cells contribute to brain tissue homeostasis and disease. Immune cell plasticity is profoundly influenced by tissue microenvironment cues and systemic factors. Aging and gut microbiota dysbiosis that reshape brain immune cell plasticity and homeostasis has not been fully delineated. Using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), we analyze compositional and transcriptional changes of the brain immune landscape in response to aging and gut dysbiosis. Discordance between canonical surface-marker-defined immune cell types and their transcriptomes suggest transcriptional plasticity among immune cells. Ly6C+ monocytes predominate a pro-inflammatory signature in the aged brain, while innate lymphoid cells (ILCs) shift toward an ILC2-like profile. Aging increases ILC-like cells expressing a T memory stemness (Tscm) signature, which is reduced through antibiotics-induced gut dysbiosis. Systemic changes due to aging and gut dysbiosis increase propensity for neuroinflammation, providing insights into gut dysbiosis in age-related neurological diseases. Golomb et al. perform cellular indexing of transcriptomes and epitopes by sequencing on immune cells from the brains of young and aged female mice with and without antibiotics-induced gut dysbiosis. Single-cell analyses reveal transcriptional plasticity of canonically identified monocytes and innate lymphoid cells in the aged brain.
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影响因子：
32.4
作者：
Colonna M
通讯作者：
Colonna M
影响因子：
64.5
作者：
Davie K;Janssens J;Koldere D;De Waegeneer M;Pech U;Kreft Ł;Aibar S;Makhzami S;Christiaens V;Bravo González-Blas C;Poovathingal S;Hulselmans G;Spanier KI;Moerman T;Vanspauwen B;Geurs S;Voet T;Lammertyn J;Thienpont B;Liu S;Konstantinides N;Fiers M;Verstreken P;Aerts S
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Aerts S
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
82.9
作者：
Gattinoni L;Speiser DE;Lichterfeld M;Bonini C
通讯作者：
Bonini C
影响因子：
32.4
作者：
Hammond, Timothy R.;Dufort, Connor;Stevens, Beth
通讯作者：
Stevens, Beth