Single-cell analysis of skeletal muscle macrophages reveals age-associated functional subpopulations

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 singl...

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Published in:eLife Vol. 11
Main Authors: Krasniewski, Linda K, Chakraborty, Papiya, Cui, Chang-Yi, Mazan-Mamczarz, Krystyna, Dunn, Christopher, Piao, Yulan, Fan, Jinshui, Shi, Changyou, Wallace, Tonya, Nguyen, Cuong, Rathbun, Isabelle A, Munk, Rachel, Tsitsipatis, Dimitrios, De, Supriyo, Sen, Payel, Ferrucci, Luigi, Gorospe, Myriam
Format: Journal Article
Language:English
Published: England eLife Sciences Publications Ltd 19.10.2022
eLife Sciences Publications, Ltd
Subjects:
Aging
Animals
Approximation
Biomarkers - metabolism
Cell adhesion & migration
Cell Biology
Cell growth
Cytokines
Flow cytometry
Gene expression
Genomics
Inflammation
Lyve1
Macrophages
Macrophages - metabolism
Male
MHCII
Mice
Muscle, Skeletal - metabolism
muscle-resident macrophages
Musculoskeletal system
Neutrophils
Ontology
Phagocytes
Phagocytes - metabolism
Proteins
Senescence
Single-Cell Analysis
Skeletal muscle
Transcriptome
Transcriptomics
mouse
Lyve1
cell biology
MHCII
flow cytometry
aging
muscle-resident macrophages
single-cell analysis
ISSN:2050-084X, 2050-084X
Online Access:Get full text
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Summary: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−/MHCII hi (M1-like, classically activated), LYVE1+/MHCII lo (M2-like, alternatively activated), and two new subgroups, LYVE1+/MHCII hi and LYVE1−/MHCII lo . Notably, one new subgroup, LYVE1+/MHCII hi , had traits of both M2 and M1 macrophages, while the other new subgroup, LYVE1−/MHCII lo , 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.
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ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.77974