Single-cell analysis of skeletal muscle macrophages reveals age-associated functional subpopulations
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PROVIDER: PRJNA800823 | ENA |
REPOSITORIES: ENA
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Project description: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 not fully understood. By single-cell transcriptomic analysis, we found that mouse SKM macrophages comprise two large populations, Lyve1+ and Lyve1-. Lyve1+ macrophages expressed high levels of mRNAs encoding angiogenesis and tissue repair proteins, while Lyve1- macrophages expressed high levels of mRNAs encoding proteins with functions in translation, antigen presentation, and the proinflammatory response. 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, all displayed strong phagocytic capacities. Flow cytometric analysis validated the presence of the four macrophage subgroups in SKM. The new subgroup Lyve1+/MHCII-hi had traits of both M2 and M1 macrophages, while the other subgroup, Lyve1-/MHCII-lo, expressed high levels of mRNAs encoding cytotoxicity proteins. In old SKM, Lyve1+/MHCII-hi macrophages were less abundant and Lyve1-/MHCII-hi macrophages were more abundant. Furthermore, complementary unsupervised classification revealed the emergence of small clusters expressing proinflammatory markers including S100a8 and S100a9 mRNAs in aged SKM. In sum, our study has identified dynamically polarized mouse SKM macrophages and a shift toward a proinflammatory status during aging.
2022-10-11 | GSE195507 | GEO
Project description: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.
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Project description:RNA sequencing of skeletal muscle macrophages
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Project description:Skeletal muscle aging is a major causative factor for disability and frailty in the elderly. Recent theories about the origins of the progressive impairment of skeletal muscle with aging emphasize a disequilibrium between damage and repair. Macrophages participate in muscle tissue repair first as pro-inflammatory M1 subtype and then as M2 anti-inflammatory subtype. However, information on macrophage presence in skeletal muscle is still sporadic and the effect of aging on different phenotypes remains unknown. In this study, we sought to characterize the polarization status of macrophages human skeletal muscle at different ages. We found that most macrophages in human skeletal muscle are M2, and that this number increased with advancing age. On the contrary, M1 macrophages decline with aging, making the total number of macrophages invariant with older age. Notably, M2 macrophages co-localized with increasing intermuscular adipose tissue (IMAT) in aging skeletal muscle. The mouse strain BALB/c, intrinsically M2-prone, showed increased IMAT and regenerating myofibers in skeletal muscle, accompanied by elevated expression of adipocyte markers and M2 cytokines. Collectively, we report that polarization of macrophages to the major M2 subtype is associated with IMAT, and propose that increased M2 in aged skeletal muscle may reflect active repair of aging-associated muscle damage.
2022-01-01 | GSE125481 | GEO
Project description:In this study, we investigated signaling pathways in Skeletal muscle precursors that are altered with aging and age-related deficits in muscle regenerative potential. We performed fluorescence activated cell sorting (FACS) to obtain highly purified skeletal muscle satellite cells from young, middle-aged and old mice. Parabiosis experiments indicate that impaired regeneration in aged mice is reversible by exposure to a young circulation, suggesting that young blood contains humoral "rejuvenating" factors that can restore regenerative function. Here, we demonstrate that the circulating protein growth differentiation factor 11 (GDF11) is a rejuvenating factor for skeletal muscle. Supplementation of systemic GDF11 levels, which normally decline with age, by heterochronic parabiosis or systemic delivery of recombinant protein, reversed functional impairments and restored genomic integrity in aged muscle stem cells (satellite cells). Increased GDF11 levels in aged mice also improved muscle structural and functional features and increased strength and endurance exercise capacity. These data indicate that GDF11 systemically regulates muscle aging and may be therapeutically useful for reversing age-related skeletal muscle and stem cell dysfunction. We used Affymetrix Mouse Genome array to identify global transcriptional changes associated with age in skeletal muscle precursors.
2014-05-08 | E-GEOD-50821 | biostudies-arrayexpress
Project description:Altered expression in sika deer skeletal muscle with age
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Project description:Tissue resident macrophages can arise from either embryonic or adult hematopoiesis and play important roles in a wide range of biological processes, such as tissue remodeling during organogenesis, tissue homeostasis in the steady state, tissue repair following injury, and immune response to pathogens. Although the origins and tissue-specific functions of resident macrophages have been extensively studied in many other tissues, they are not well characterized in skeletal muscle. In the present study, we have characterized for the first time the ontogeny of skeletal muscle resident macrophages, showing evidence that they arise from both embryonic hematopoietic progenitors, including yolk sac primitive macrophages and fetal liver monocytes, and adult bone marrow hematopoietic stem cells. Single cell-based transcriptome analysis revealed that skeletal muscle resident macrophages were highly distinctive from resident macrophages in other tissues, expressing a specific set of transcription factors and containing functionally diverse subsets correlating to their origins. They appear more active in maintaining tissue homeostasis and promoting muscle growth and regeneration.
2020-07-29 | GSE142480 | GEO
Project description:Loss of muscle mass and function—a hallmark of skeletal muscle aging—is known as sarcopenia. Moreover, mammalian aging is reportedly driven by loss of epigenetic information. However, the effect of epigenetic alterations on skeletal muscle homeostasis is unknown. In this study, we show that chronic elevation of global DNA methylation results in a myopathy-like phenotype and age-related changes in skeletal muscle. Overexpression of muscle de novo methyltransferase 3a (Dnmt3a) increased central nucleus-positive myofibers, predominantly in fast-twitch myofibers, and shifted muscle fiber type to stress-resistant slow-twitch myofibers, accompanied by upregulation of chemokine and immune system-related genes and reduced basal autophagy in skeletal muscle. Dnmt3a overexpression reduced muscle androgen receptor signaling, decreased muscle mass and strength, and impaired tolerance to endurance exercise with age. Network analysis identified Akt1 as a potential hub gene. Dnmt3a expression reduced sensitivity to starvation-induced muscle atrophy by suppressing the FoxO-regulated autophagy and ubiquitin–proteasome systems. These data suggest that increased global DNA methylation disrupts skeletal muscle homeostasis, promotes age-related decline in muscle function, and reduces muscle plasticity.
2025-01-16 | GSE244432 | GEO
Project description:Healthy human skeletal muscle samples were processed and analyzed to infer age associated skeletal muscle changes.
2020-04-07 | GSE129643 | GEO
Project description:In this study, we investigated signaling pathways in Skeletal muscle precursors that are altered with aging and age-related deficits in muscle regenerative potential. We performed fluorescence activated cell sorting (FACS) to obtain highly purified skeletal muscle satellite cells from young, middle-aged and old mice. Parabiosis experiments indicate that impaired regeneration in aged mice is reversible by exposure to a young circulation, suggesting that young blood contains humoral "rejuvenating" factors that can restore regenerative function. Here, we demonstrate that the circulating protein growth differentiation factor 11 (GDF11) is a rejuvenating factor for skeletal muscle. Supplementation of systemic GDF11 levels, which normally decline with age, by heterochronic parabiosis or systemic delivery of recombinant protein, reversed functional impairments and restored genomic integrity in aged muscle stem cells (satellite cells). Increased GDF11 levels in aged mice also improved muscle structural and functional features and increased strength and endurance exercise capacity. These data indicate that GDF11 systemically regulates muscle aging and may be therapeutically useful for reversing age-related skeletal muscle and stem cell dysfunction.
2014-05-08 | GSE50821 | GEO