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Pro-inflammatory macrophages impair skeletal muscle regeneration in ischemic-damaged limbs by inducing precocious differentiation of satellite cells [scRNA-seq]

ABSTRACT: To investigate the molecular mechanisms responsible for failed skeletal muscle repair in the Chronic limb threatening ischemia (CLTI) limb. We used single cell RNA sequencing (scRNA-seq) to profile the transcriptomes of the skeletal muscle specimens.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE227075 | GEO | 2023/10/16

REPOSITORIES: GEO

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Pro-inflammatory macrophages impair skeletal muscle regeneration in ischemic-damaged limbs by inducing precocious differentiation of satellite cells [RNA-seq]

Project description:To validate the findings from scRNA-seq, we purified CD11b+/F480+ macrophages by FACS from the hind limb muscle of C57BL/6 (n=3) and BALB/c (n=2) mice at 3-days post HLI for bulk RNA-seq analysis We then performed gene expression profiling analysis using data obtained from RNA-seq of isolated macrophages from C57BL/6 and BALB/c mice at day 3 after HLI surgery.

2023-10-16 | GSE227076 | GEO

Pro-inflammatory macrophages impair skeletal muscle regeneration in ischemic-damaged limbs by inducing precocious differentiation of satellite cells [scRNA-seq]

Project description:Pro-inflammatory macrophages impair skeletal muscle regeneration in ischemic-damaged limbs by inducing precocious differentiation of satellite cells [scRNA-seq]

| PRJNA943182 | ENA

Pro-inflammatory macrophages impair skeletal muscle regeneration in ischemic-damaged limbs by inducing precocious differentiation of satellite cells [RNA-seq]

Project description:Pro-inflammatory macrophages impair skeletal muscle regeneration in ischemic-damaged limbs by inducing precocious differentiation of satellite cells [RNA-seq]

| PRJNA943181 | ENA

Skeletal muscle regeneration failure in ischemic-damaged limbs is associated with pro-inflammatory macrophages and premature differentiation of satellite cells.

Project description:BackgroundChronic limb-threatening ischemia (CLTI), a severe manifestation of peripheral arterial disease (PAD), is associated with a 1-year limb amputation rate of approximately 15-20% and substantial mortality. A key feature of CLTI is the compromised regenerative ability of skeletal muscle; however, the mechanisms responsible for this impairment are not yet fully understood. In this study, we aim to delineate pathological changes at both the cellular and transcriptomic levels, as well as in cell-cell signaling pathways, associated with compromised muscle regeneration in limb ischemia in both human tissue samples and murine models of CLTI.MethodsWe performed single-cell transcriptome analysis of ischemic and non-ischemic muscle from the same CLTI patients and from a murine model of CLTI. In both datasets, we analyzed gene expression changes in macrophage and muscle satellite cell (MuSC) populations as well as differential cell-cell signaling interactions and differentiation trajectories.ResultsSingle-cell transcriptomic profiling and immunofluorescence analysis of CLTI patient skeletal muscle demonstrated that ischemic-damaged tissue displays a pro-inflammatory macrophage signature. Comparable results were observed in a murine CLTI model. Moreover, integrated analyses of both human and murine datasets revealed premature differentiation of MuSCs to be a key feature of failed muscle regeneration in the ischemic limb. Furthermore, in silico inferences of intercellular communication and in vitro assays highlight the importance of macrophage-MuSC signaling in ischemia induced muscle injuries.ConclusionsCollectively, our research provides the first single-cell transcriptome atlases of skeletal muscle from CLTI patients and a murine CLTI model, emphasizing the crucial role of macrophages and inflammation in regulating muscle regeneration in CLTI through interactions with MuSCs.

| S-EPMC10636829 | biostudies-literature

The muscle proteome reflects changes in mitochondrial function, cellular stress and proteolysis after 14 days of unilateral lower limb immobilization in active young men

Project description:Skeletal muscle unloading due to joint immobilization induces skeletal muscle atrophy. However, the skeletal muscle proteome response to limb immobilization has not been investigated using SWATH methods. This study quantitatively characterized the muscle proteome at baseline, and after 3 and 14 d of unilateral lower limb (knee-brace) immobilization in 18 healthy young men (25.4 ±5.5 y, 81.2 ±11.6 kg). All muscle biopsies were obtained from the vastus lateralis muscle. Unilateral lower limb immobilization was preceded by four-weeks of exercise training to standardise acute training history, and 7 days of dietary provision to standardise energy/macronutrient intake. Dietary intake was also standardised/provided throughout the 14 d immobilization period.

2022-08-25 | PXD034908 | Pride

Skeletal muscle regeneration failure in ischemic-damaged limbs is associated with pro-inflammatory macrophages and premature differentiation of satellite cells

Project description:Skeletal muscle regeneration failure in ischemic-damaged limbs is associated with pro-inflammatory macrophages and premature differentiation of satellite cells

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Muscle SATellite cell study (MSAT)

Project description:Skeletal muscle fiber type distribution has implications for human health, muscle function and performance. This knowledge has been gathered using labor-intensive and costly methodology that limited these studies. This data was used to present a new method based on muscle tissue RNA sequencing data to estimate the distribution of skeletal muscle fiber types from frozen human samples, allowing for larger number of individuals to be tested in a cost and labor efficient way. Muscle biopsies were taken from the vastus lateralis muscle of 39 Swedish male subjects. Samples were sequenced on the NextSeqÃ‚Â® 500/550 (Illumina).

| EGAS00001006363 | EGA

Skeletal muscle regeneration failure in ischemic-damaged limbs is associated with pro-inflammatory macrophages and premature differentiation of satellite cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-10-16 | GSE227077 | GEO

Pharyngeal Satellite Cell Expression Profile

Project description:To compare the differential gene expression between sorted satellite cells collected from pharyngeal verses limb muscle.

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Expression profiles of satellite cells and alpha7Sca1 cells in mdxITGAM-DTR mice

Project description:We took advantage of a dystrophic mouse model of transient macrophage-depletion, mdxITGAM-DTR mice, in order to analyze the role of macrophage in skeletal muscle regeneration. We generated the transcriptome of satellite cells (SCs) and alpha7Sca1 cells purified by cell sorting from mdxITGAM-DTR mice. The mice were treated, by intramuscular injection, with PBS, as vehicle, or with Diphtheria toxin (DT) in order to achieve the macrophage depletion form hind-limb muscle We described a shift in identity of muscle stem cells dependent on the crosstalk between macrophages and satellite cells. Indeed macrophage depletion determines an exacerbated dystrophic phenotype associated with adipogenic conversion of SCs and reduction of the SC pool.

2019-09-17 | GSE134770 | GEO

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