Single cell transcriptome analysis identified a unique neutrophil type associated with Alzheimer's disease.

IF 5.2 2区医学 Q1 GERIATRICS & GERONTOLOGY Immunity & Ageing Pub Date : 2024-06-25 DOI:10.1186/s12979-024-00448-x

Xiaolin Zhang, Guiqin He, Yixuan Hu, Boren Liu, Yuliang Xu, Xia Li, Xinyou Lv, Jin Li

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Abstract

Background: Neutrophils play an essential role in Alzheimer's disease (AD) pathology. However, the extent of their heterogeneity remains poorly explored, particularly in the context of developing novel therapies targeting these cells.

Results: We investigate the population structure of neutrophils purified from peripheral blood samples of AD mice. Utilizing single cell RNA sequencing, we comprehensively map neutrophil populations into six distinct clusters and find that the Neu-5 subset is specially enriched in AD mice. This subset exhibits fewer specific granules and a lower mature score. Gene ontology (GO) analysis reveals that genes involved in cytokine-mediated signaling are downregulated in the Neu-5 cluster. Furthermore, we identify the Ccrl2 gene is specifically upregulated in this subgroup, which is confirmed by flow cytometry in AD mice. Finally, immunohistochemical staining indicates that CCRL2 protein is increased in the brains of AD mice.

Conclusions: We identify a unique CCRL2 positive neutrophil cluster, that is specifically enriched in the peripheral blood of AD mice.

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单细胞转录组分析确定了一种与阿尔茨海默病相关的独特中性粒细胞类型。

背景：中性粒细胞在阿尔茨海默病（AD）病理学中扮演着重要角色。然而，人们对中性粒细胞异质性的程度仍缺乏深入研究，尤其是在开发针对这些细胞的新型疗法方面：我们研究了从 AD 小鼠外周血样本中纯化的中性粒细胞的群体结构。利用单细胞 RNA 测序技术，我们将中性粒细胞群体全面映射为六个不同的集群，并发现 Neu-5 亚群在 AD 小鼠中特别富集。该亚群表现出较少的特异性颗粒和较低的成熟度。基因本体（GO）分析表明，参与细胞因子介导的信号转导的基因在Neu-5集群中下调。此外，我们还发现 Ccrl2 基因在该亚群中特异性上调，这一点在 AD 小鼠的流式细胞术中得到了证实。最后，免疫组化染色表明，AD 小鼠大脑中的 CCRL2 蛋白增加：结论：我们发现了一个独特的 CCRL2 阳性中性粒细胞集群，该集群特异性地富集于 AD 小鼠的外周血中。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY

CiteScore

10.20

自引率

3.80%

发文量

期刊介绍： Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.