Characterizing Macrophage Diversity in Metastasis-Bearing Lungs Reveals a Lipid-Associated Macrophage Subset.
Characterizing Macrophage Diversity in Metastasis-Bearing Lungs Reveals a Lipid-Associated Macrophage Subset.
复制标题
表征转移性肺中巨噬细胞多样性揭示了脂质相关巨噬细胞亚群。
DOI：
10.1158/0008-5472.can-21-0101
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发表时间：
2021-10-15
期刊：
影响因子：
11.2
通讯作者：
Schwertfeger KL
中科院分区：
文献类型：
--
作者：
Huggins DN;LaRue RS;Wang Y;Knutson TP;Xu Y;Williams JW;Schwertfeger KL
虽然巨噬细胞是在原发性和转移性乳腺肿瘤中发现的最丰富的免疫细胞类型之一，但它们的复杂性和异质性如何随着转移进展而变化仍然未知。在这里，巨噬细胞被分离出的小鼠的肺原位乳腺肿瘤单细胞RNA测序。鉴定了7个不同的巨噬细胞簇，包括表现出与抗原呈递（H2-Aa，Cd 74）、细胞周期（Stmn 1，Cdk 1）和干扰素信号传导（Isg 15，Ifitm 3）相关的基因的增强的差异表达的群体。有趣的是，一个簇表现出与脂质相关巨噬细胞（Lgals 3，Trem 2）一致的特征。与非荷瘤对照相比，荷瘤小鼠肺部每克组织中这些细胞的数量显着增加，其中绝大多数与肺泡巨噬细胞标记物Siglec-F共染色呈阳性。观察到与脂质代谢以及细胞外基质重塑和免疫抑制相关的途径中涉及的基因的富集。此外，这些细胞显示吞噬能力降低。总的来说，这些发现突出了转移性病变内存在的巨噬细胞的多样性，并表征了先前在肺转移瘤中未识别的脂质相关巨噬细胞亚群。
While macrophages are among the most abundant immune cell type found within primary and metastatic mammary tumors, how their complexity and heterogeneity change with metastatic progression remains unknown. Here, macrophages were isolated from the lungs of mice bearing orthotopic mammary tumors for single-cell RNA sequencing. Seven distinct macrophage clusters were identified, including populations exhibiting enhanced differential expression of genes related to antigen presentation (H2-Aa, Cd74), cell cycle (Stmn1, Cdk1), and interferon signaling (Isg15, Ifitm3). Interestingly, one cluster demonstrated a profile concordant with lipid-associated macrophages (Lgals3, Trem2). Compared to non-tumor-bearing controls, the number of these cells per gram of tissue was significantly increased in lungs from tumor-bearing mice, with the vast majority co-staining positively with the alveolar macrophage marker Siglec-F. Enrichment of genes implicated in pathways related to lipid metabolism as well extracellular matrix remodeling and immunosuppression was observed. Additionally, these cells displayed reduced capacity for phagocytosis. Collectively, these findings highlight the diversity of macrophages present within metastatic lesions and characterize a lipid-associated macrophage subset previously unidentified in lung metastases.