Single-cell analysis of skeletal muscle macrophages reveals age-associated functional subpopulations.
Single-cell analysis of skeletal muscle macrophages reveals age-associated functional subpopulations.
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DOI：
10.7554/elife.77974
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发表时间：
2022-10-19
期刊：
影响因子：
7.7
通讯作者：
Gorospe M
中科院分区：
文献类型：
--
作者：
Krasniewski LK;Chakraborty P;Cui CY;Mazan-Mamczarz K;Dunn C;Piao Y;Fan J;Shi C;Wallace T;Nguyen C;Rathbun IA;Munk R;Tsitsipatis D;De S;Sen P;Ferrucci L;Gorospe M
组织驻留巨噬细胞代表一组高度反应的天然免疫细胞，通过极化不同的亚群获得不同的功能。骨骼肌(SKM)中的巨噬细胞亚群及其在衰老过程中的变化特征尚不清楚。通过非监督聚类的单细胞转录分析，我们在雄性小鼠SKM中发现了11个不同的巨噬细胞簇，其丰富的基因表达程序与修复、促炎、吞噬、增殖和衰老相关功能有关。利用互补分类，膜标记LYVE1和MHCII鉴定了四个巨噬细胞亚群：LYVE1−/MHCIIHi(类似M1，经典激活)，LYVE1+/MHCIIlo(类似M2，交替激活)，以及两个新亚群，LYVE1+/MHCIIHi和LYVE1−/MHCIIlo。值得注意的是，一个新的亚群LYVE1+/MHCIIHi同时具有M2和M1巨噬细胞的特征，而另一个新的亚群LYVE1−/MHCIIlo表现出很强的吞噬能力。流式细胞仪分析证实了上述4种巨噬细胞亚群的存在，并发现LYVE1−巨噬细胞比LYVE1+巨噬细胞在老年SKM中更为丰富。在老年小鼠的巨噬细胞簇中，促炎症标志物(S100A8和S100A9 mRNAs)和衰老相关标志物(GPNMB和Spp1 mRNAs)明显增加。总之，我们鉴定了动态极化的SKM巨噬细胞，并提出特定的巨噬细胞亚群与陈旧性SKM的促炎和衰老特征有关。
Tissue-resident macrophages represent a group of highly responsive innate immune cells that acquire diverse functions by polarizing toward distinct subpopulations. The subpopulations of macrophages that reside in skeletal muscle (SKM) and their changes during aging are poorly characterized. By single-cell transcriptomic analysis with unsupervised clustering, we found 11 distinct macrophage clusters in male mouse SKM with enriched gene expression programs linked to reparative, proinflammatory, phagocytic, proliferative, and senescence-associated functions. Using a complementary classification, membrane markers LYVE1 and MHCII identified four macrophage subgroups: LYVE1−/MHCIIhi (M1-like, classically activated), LYVE1+/MHCIIlo (M2-like, alternatively activated), and two new subgroups, LYVE1+/MHCIIhi and LYVE1−/MHCIIlo. Notably, one new subgroup, LYVE1+/MHCIIhi, had traits of both M2 and M1 macrophages, while the other new subgroup, LYVE1−/MHCIIlo, displayed strong phagocytic capacity. Flow cytometric analysis validated the presence of the four macrophage subgroups in SKM and found that LYVE1− macrophages were more abundant than LYVE1+ macrophages in old SKM. A striking increase in proinflammatory markers (S100a8 and S100a9 mRNAs) and senescence-related markers (Gpnmb and Spp1 mRNAs) was evident in macrophage clusters from older mice. In sum, we have identified dynamically polarized SKM macrophages and propose that specific macrophage subpopulations contribute to the proinflammatory and senescent traits of old SKM.
影响因子：
2.3
作者：
Blackwell, Jamie;Harries, Lorna W.;Pilling, Luke C.;Ferrucci, Luigi;Jones, Andrew;Melzer, David
通讯作者：
Melzer, David