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 towards distinct subgroups. The subgroups of macrophages that reside in skeletal muscle (SKM) and their changes during aging are poorly characterized. By single-cell tr...

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Hlavní autori: Krasniewski, Linda K, Chakraborty, Papiya, Chang-Yi, Cui, 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 M
Médium: Paper
Jazyk:English
Vydavateľské údaje: Cold Spring Harbor Cold Spring Harbor Laboratory Press 24.02.2022
Cold Spring Harbor Laboratory
Vydanie:1.1
Predmet:
Aging
Cell Biology
Cell surface
Cytotoxicity
Flow cytometry
Inflammation
Macrophages
Musculoskeletal system
Skeletal muscle
Surface markers
Transcriptomics
macrophages
polarization
aging
Skeletal muscle
single-cell analysis
ISSN:2692-8205, 2692-8205
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Abstract Tissue-resident macrophages represent a group of highly responsive innate immune cells that acquire diverse functions by polarizing towards distinct subgroups. The subgroups of macrophages that reside in skeletal muscle (SKM) and their changes during aging are poorly characterized. By single-cell transcriptomic analysis, we found that mouse SKM macrophages primarily comprise two large populations, “healing” LYVE1+ and “proinflammatory” LYVE1-macrophages. SKM macrophages were further classified into four functional subgroups based on the expression levels of another cell-surface marker, MHCII: LYVE1+/MHCII-lo (similar to alternatively activated M2), LYVE1-/MHCII-hi (similar to classically activated M1), and two new subgroups, LYVE1+/MHCII-hi and LYVE1-/MHCII-lo. Notably, the new subgroup LYVE1+/MHCII-hi had traits of both M2 and M1 macrophages, while the other new subgroup, LYVE1-/MHCII-lo, expressed high levels of mRNAs encoding cytotoxicity proteins. Flow cytometric analysis validated the presence of the four macrophage subgroups in SKM. In old SKM, LYVE1- macrophages were more abundant than LYVE1+ macrophages. Furthermore, complementary unsupervised classification revealed the emergence of specific macrophage subclusters expressing abundant proinflammatory markers, including S100a8 and S100a9 in aged SKM. In sum, our study has identified dynamically polarized mouse SKM macrophages and further uncovered the contribution of specific macrophage subpopulations to the proinflammatory status in old SKM. Competing Interest Statement The authors have declared no competing interest.
AbstractList Tissue-resident macrophages represent a group of highly responsive innate immune cells that acquire diverse functions by polarizing towards distinct subgroups. The subgroups of macrophages that reside in skeletal muscle (SKM) and their changes during aging are poorly characterized. By single-cell transcriptomic analysis, we found that mouse SKM macrophages primarily comprise two large populations, “healing” LYVE1+ and “proinflammatory” LYVE1-macrophages. SKM macrophages were further classified into four functional subgroups based on the expression levels of another cell-surface marker, MHCII: LYVE1+/MHCII-lo (similar to alternatively activated M2), LYVE1-/MHCII-hi (similar to classically activated M1), and two new subgroups, LYVE1+/MHCII-hi and LYVE1-/MHCII-lo. Notably, the new subgroup LYVE1+/MHCII-hi had traits of both M2 and M1 macrophages, while the other new subgroup, LYVE1-/MHCII-lo, expressed high levels of mRNAs encoding cytotoxicity proteins. Flow cytometric analysis validated the presence of the four macrophage subgroups in SKM. In old SKM, LYVE1- macrophages were more abundant than LYVE1+ macrophages. Furthermore, complementary unsupervised classification revealed the emergence of specific macrophage subclusters expressing abundant proinflammatory markers, including S100a8 and S100a9 in aged SKM. In sum, our study has identified dynamically polarized mouse SKM macrophages and further uncovered the contribution of specific macrophage subpopulations to the proinflammatory status in old SKM. Competing Interest Statement The authors have declared no competing interest.
Tissue-resident macrophages represent a group of highly responsive innate immune cells that acquire diverse functions by polarizing towards distinct subgroups. The subgroups of macrophages that reside in skeletal muscle (SKM) and their changes during aging are poorly characterized. By single-cell transcriptomic analysis, we found that mouse SKM macrophages primarily comprise two large populations, “healing” LYVE1+ and “proinflammatory” LYVE1-macrophages. SKM macrophages were further classified into four functional subgroups based on the expression levels of another cell-surface marker, MHCII: LYVE1+/MHCII-lo (similar to alternatively activated M2), LYVE1-/MHCII-hi (similar to classically activated M1), and two new subgroups, LYVE1+/MHCII-hi and LYVE1-/MHCII-lo. Notably, the new subgroup LYVE1+/MHCII-hi had traits of both M2 and M1 macrophages, while the other new subgroup, LYVE1-/MHCII-lo, expressed high levels of mRNAs encoding cytotoxicity proteins. Flow cytometric analysis validated the presence of the four macrophage subgroups in SKM. In old SKM, LYVE1-macrophages were more abundant than LYVE1+ macrophages. Furthermore, complementary unsupervised classification revealed the emergence of specific macrophage subclusters expressing abundant proinflammatory markers, including S100a8 and S100a9 in aged SKM. In sum, our study has identified dynamically polarized mouse SKM macrophages and further uncovered the contribution of specific macrophage subpopulations to the proinflammatory status in old SKM.
Author Fan, Jinshui
Mazan-Mamczarz, Krystyna
Rathbun, Isabelle A
Chang-Yi, Cui
Nguyen, Cuong
De, Supriyo
Sen, Payel
Chakraborty, Papiya
Shi, Changyou
Piao, Yulan
Gorospe, Myriam M
Krasniewski, Linda K
Wallace, Tonya
Tsitsipatis, Dimitrios
Dunn, Christopher
Ferrucci, Luigi
Munk, Rachel
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Cites_doi 10.21769/BioProtoc.3984
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Copyright 2022. This article is published under https://creativecommons.org/publicdomain/zero/1.0/ (“the License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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Keywords macrophages
polarization
aging
Skeletal muscle
single-cell analysis
Language English
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Competing Interest Statement: The authors have declared no competing interest.
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Snippet Tissue-resident macrophages represent a group of highly responsive innate immune cells that acquire diverse functions by polarizing towards distinct subgroups....
SourceID biorxiv
proquest
SourceType Open Access Repository
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SubjectTerms Aging
Cell Biology
Cell surface
Cytotoxicity
Flow cytometry
Inflammation
Macrophages
Musculoskeletal system
Skeletal muscle
Surface markers
Transcriptomics
Title Single-cell analysis of skeletal muscle macrophages reveals age- associated functional subpopulations
URI https://www.proquest.com/docview/2632511099
https://www.biorxiv.org/content/10.1101/2022.02.23.481581
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