ArticleGenome medicine2023
Skeletal muscle regeneration failure in ischemic-damaged limbs is associated with pro-inflammatory macrophages and premature differentiation of satellite cells.
Article in Genome medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 38 citations in OpenAlex.
- A cardiovascular-motor axis framework for perfusion-mediated motor impairment.International journal of cardiology. Heart & vasculature · 2026Review
- 3D bioprinted human vascular organoid sheets promote functional ischemic repair and exhibit adaptive in vivo remodeling.BMC medicine · 2026Article
- Impaired Myogenic Differentiation Is a Shared Feature Across Genetic Myopathies.International journal of molecular sciences · 2026Review
- The cellular ecosystem of skeletal muscle regeneration: molecular mechanisms, pathological disorders, and potential therapeutic strategies.Stem cell research & therapy · 2026Review
- Intramuscular Adipose Tissue Accumulation is a Key Determinant of Limb Function in Peripheral Artery Disease.Circulation · 2026Article
- Single-Cell Transcriptomic Analysis Reveals Multicellular Coordination and Signaling Rewiring During Fetal Goat Skeletal Muscle Development.Animals : an open access journal from MDPI · 2026Article
- Diabetes-induced TREM2-endothelial cell signaling impairs ischemic vascular repair.Science translational medicine · 2026Article
- The role of the cGAS/STING pathway in skeletal muscle regeneration: modulation of inflammation, macrophage polarization, and oxidative stress.Cellular & molecular biology letters · 2026Article
- Targeting Arterial Dysfunction in Cardiovascular Disease Using Stem Cell-Based Therapies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Cannabinoid type 2 receptor regulates skeletal muscle regeneration by NLRP3-GSDMD mediated macrophage pyroptosis after injury.Cell death discovery · 2026Article
- A Borophosphate Glass Doped with Cobalt Oxide Improves Skeletal Muscle Structure and Function in Myopathic Mice.Journal of functional biomaterials · 2026Article
- Phosphodiesterase 4 (PDE 4) Inhibition Reduces Ischemia-Reperfusion-Induced Leucocyte Infiltration, Apoptosis and Mitochondrial Fission Markers in Mice Skeletal Muscles Four Hours After Ischemia Onset.Muscles (Basel, Switzerland) · 2026Article
- Activin A secretion by muscle-repairing macrophages induces heterotopic ossification in mice.The Journal of clinical investigation · 2026Article
- Intramuscular Adipose Tissue Accumulation is a Key Determinant of Limb Function in Peripheral Artery Disease.bioRxiv : the preprint server for biology · 2026Article
- New Insights into Neuromuscular Junction Biology: Evidence from Human and Animal Research.International journal of molecular sciences · 2026Review
- The ageing microenvironment in sarcopenia: early alterations and targeted therapeutic strategies.Frontiers in immunology · 2026Review
- Variant-to-Biomarker Pathways in Peripheral Artery Disease: Multiomics Integration and Clinical Translation.Human mutation · 2026Review
- Nanoengineered GATA3International journal of nanomedicine · 2026Article
- Multi-omics integration reveals macrophage polarization and ferroptosis as key mechanisms underlying kaempferol's therapeutic efficacy in peripheral artery disease.Frontiers in immunology · 2026Article
- Effect of Allogenic Mesenchymal Stem Cell Injection on Functional Repair Outcomes Following Skeletal Muscle Laceration Injury.Biomedicines · 2025Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
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.
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