ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2021
Gli1 Defines a Subset of Fibro-adipogenic Progenitors that Promote Skeletal Muscle Regeneration With Less Fat Accumulation.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 36 citations in OpenAlex.
- The Primary Cilium: A New Player in Muscle Stem Cell Biology.Stem cell reviews and reports · 2026Review
- Hedgehog/GLI Signaling at the Interface of Sterol Metabolism, Mitochondrial ROS Signaling and Cellular Plasticity.Antioxidants (Basel, Switzerland) · 2026Review
- The cellular ecosystem of skeletal muscle regeneration: molecular mechanisms, pathological disorders, and potential therapeutic strategies.Stem cell research & therapy · 2026Review
- Mouse Models of Muscle Fibrosis: Mechanisms, Methods, and Applications.Biomedicines · 2026Review
- Platelet-rich plasma-derived exosomes establishing a muscular proregenerative microenvironment through enhancing the viability of fibro-adipogenic progenitors.Experimental & molecular medicine · 2025Article
- GNAS/PKA signaling promotes aberrant osteochondral differentiation of Gli1The EMBO journal · 2025Article
- From fibro/adipogenic progenitors to adipocytes: Understanding adipogenesis in muscle degeneration for disease modulation.The Journal of physiology · 2025Review
- Intramuscular adipose tissue: from progenitor to pathology.American journal of physiology. Cell physiology · 2025Review
- Ablation of UCP-1+ cells impacts FAP dynamics in muscle regeneration.American journal of physiology. Cell physiology · 2025Article
- Article
- Integrating spatial and single-cell transcriptomics to characterize mouse long bone fracture healing process.Communications biology · 2025Article
- PdgfrαGenes & diseases · 2025Review
- Gli1 regulates fibro/adipogenic progenitor function through modulation of Ido1 in muscle regeneration.International journal of biological sciences · 2025Article
- Fibro-adipogenic progenitor cells in skeletal muscle unloading: metabolic and functional impairments.Skeletal muscle · 2024Article
- Molecular mechanism of skeletal muscle loss and its prevention by natural resources.Food science and biotechnology · 2024Review
- Fibro-adipogenic progenitors in physiological adipogenesis and intermuscular adipose tissue remodeling.Molecular aspects of medicine · 2024Review
- A role for TGFβ signaling in Gli1+ tendon and enthesis cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Cellular interactions and microenvironment dynamics in skeletal muscle regeneration and disease.Frontiers in cell and developmental biology · 2024Review
- Gli1 marks a sentinel muscle stem cell population for muscle regeneration.Nature communications · 2023Article
- Thrown for a loop: fibro-adipogenic progenitors in skeletal muscle fibrosis.American journal of physiology. Cell physiology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Skeletal muscle has remarkable regenerative ability after injury. Mesenchymal fibro-adipogenic progenitors (FAPs) are necessary, active participants during this repair process, but the molecular signatures of these cells and their functional relevance remain largely unexplored. Here, using a lineage tracing mouse model (Gli1-CreER Tomato), we demonstrate that Gli1 marks a small subset of muscle-resident FAPs with elevated Hedgehog (Hh) signaling. Upon notexin muscle injury, these cells preferentially and rapidly expanded within FAPs. Ablation of Gli1+ cells using a DTA mouse model drastically reduced fibroblastic colony-forming unit (CFU-F) colonies generated by muscle cells and impaired muscle repair at 28 days. Pharmacologic manipulation revealed that Gli1+ FAPs rely on Hh signaling to increase the size of regenerating myofiber. Sorted Gli1+ FAPs displayed superior clonogenicity and reduced adipogenic differentiation ability in culture compared to sorted Gli1- FAPs. In a glycerol injury model, Gli1+ FAPs were less likely to give rise to muscle adipocytes compared to other FAPs. Further cell ablation and Hh activator/inhibitor treatments demonstrated their dual actions in enhancing myogenesis and reducing adipogenesis after injury. Examining single-cell RNA-sequencing dataset of FAPs from normal mice indicated that Gli1+ FAPs with increased Hh signaling provide trophic signals to myogenic cells while restrict their own adipogenic differentiation. Collectively, our findings identified a subpopulation of FAPs that play an essential role in skeletal muscle repair. © 2021 American Society for Bone and Mineral Research (ASBMR).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.