Academic literature on the topic 'Fibro-adipogenic progenitor'
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Journal articles on the topic "Fibro-adipogenic progenitor"
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Subhash, Ajith K., Michael Davies, Andrew Gatto, et al. "Fibro-adipogenesis in Injured Rotator Cuff Muscle." Current Tissue Microenvironment Reports 3, no. 1 (2022): 1–9. http://dx.doi.org/10.1007/s43152-021-00033-0.
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Abstract Purpose of Review Fibro-adipogenic progenitors were first characterized in 2010 and later found to contribute significantly to muscle regeneration and mediate degenerative changes in muscle following injury. These progenitors were also found to have an influence on the rotator cuff muscle’s response to chronic injury which is defined by fibrosis accompanied by massive fatty degeneration. The purpose of this review is to highlight progenitor cells, their contribution to fibro-adipogenesis in rotator cuff tissue, and the factors influencing fibro-adipogenesis in this tissue. Recent Findings Fibro-adipogenic progenitors are a key mediator of the fatty infiltration notably prevalent in rotator cuff injury. Relative to other muscle groups, the rotator cuff has relatively high rates of fibro-adipogenesis following massive chronic rotator cuff tears. This may be linked to the pre-injury density of fibro-adipogenic progenitors in muscle tissue affecting post-injury levels of fibro-adipogenesis. In addition, suprascapular nerve injury in rat models of rotator cuff tears has demonstrated worse, histologic, and biomechanical properties and lower healing rates of rotator cuff repairs. However, fatty infiltration in the rotator cuff following suprascapular nerve compression has been shown to be reversible following release of the nerve compression. Summary The fibro-adipogenic response to acute and chronic injury in rotator cuff tissue is determined by a complex array of factors including progenitor cell influence, transcriptional pathways, chronicity of the injury, anatomic location of injury, microenvironmental influences, and the severity of nerve involvement. Elucidating the complex interactions of these factors will provide potential targets for therapeutic intervention in vivo.
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Sono, Takashi, Ching-Yun Hsu, Yiyun Wang, et al. "Perivascular Fibro-Adipogenic Progenitor Tracing during Post-Traumatic Osteoarthritis." American Journal of Pathology 190, no. 9 (2020): 1909–20. http://dx.doi.org/10.1016/j.ajpath.2020.05.017.
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Reggio, Alessio, Marco Rosina, Natalie Krahmer, et al. "Metabolic reprogramming of fibro/adipogenic progenitors facilitates muscle regeneration." Life Science Alliance 3, no. 3 (2020): e202000646. http://dx.doi.org/10.26508/lsa.202000660.
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In Duchenne muscular dystrophy (DMD), the absence of the dystrophin protein causes a variety of poorly understood secondary effects. Notably, muscle fibers of dystrophic individuals are characterized by mitochondrial dysfunctions, as revealed by a reduced ATP production rate and by defective oxidative phosphorylation. Here, we show that in a mouse model of DMD (mdx), fibro/adipogenic progenitors (FAPs) are characterized by a dysfunctional mitochondrial metabolism which correlates with increased adipogenic potential. Using high-sensitivity mass spectrometry–based proteomics, we report that a short-term high-fat diet (HFD) reprograms dystrophic FAP metabolism in vivo. By combining our proteomic dataset with a literature-derived signaling network, we revealed that HFD modulates the β-catenin–follistatin axis. These changes are accompanied by significant amelioration of the histological phenotype in dystrophic mice. Transplantation of purified FAPs from HFD-fed mice into the muscles of dystrophic recipients demonstrates that modulation of FAP metabolism can be functional to ameliorate the dystrophic phenotype. Our study supports metabolic reprogramming of muscle interstitial progenitor cells as a novel approach to alleviate some of the adverse outcomes of DMD.
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Wan, Renwen, Hanli Zhang, Shan Liu, et al. "Role of fibro-adipogenic progenitors in skeletal muscle aging." Aging Pathobiology and Therapeutics 5, no. 2 (2023): 72–78. http://dx.doi.org/10.31491/apt.2023.06.116.
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Maintaining muscle mass is of paramount importance from a clinical perspective as it supports the flexibility, strength, and essential daily tasks that the body requires. Furthermore, muscle plays a role in regulating the body’s metabolic system. Unfortunately, aging can lead to a loss of muscle mass, which can reduce personal independence and quality of life while increasing the risk of developing disease. Fibro-adipogenic progenitor cells (FAPs) are muscle-resident progenitor cells that are essential for maintaining skeletal muscle fiber size and muscle regeneration. These vital FAP functions are mediated by a complex secretome that interacts in a paracrine manner to promote the division and differentiation of muscle satellite cells. Dysregulated differentiation of FAPs can lead to fibrosis, fatty infiltration, muscle atrophy, and poor muscle regeneration. In this article, we review what is currently known about how FAPs function in aging muscle and how they may prevent the onset of muscle wasting and degeneration. Finally, we discuss how FAPs represent a population of cells that can be used as therapeutic targets to improve the health of skeletal and muscle tissues as they age.
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Parker, Emily, and Mark W. Hamrick. "Role of fibro-adipogenic progenitor cells in muscle atrophy and musculoskeletal diseases." Current Opinion in Pharmacology 58 (June 2021): 1–7. http://dx.doi.org/10.1016/j.coph.2021.03.003.
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Jay, J. H., M. Liu, X. Liu, B. T. Feeley, and C. S. Sabatini. "Does the Antimalarial Drug Quinine Contribute to Muscle Fibro/Adipogenic Progenitor Fibrogenesis?" Muscle Ligaments and Tendons Journal 11, no. 04 (2021): 635. http://dx.doi.org/10.32098/mltj.04.2021.04.
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Guilhot, Corentin, Théo Fovet, Pierre Delobel, et al. "Severe Muscle Deconditioning Triggers Early Extracellular Matrix Remodeling and Resident Stem Cell Differentiation into Adipocytes in Healthy Men." International Journal of Molecular Sciences 23, no. 10 (2022): 5489. http://dx.doi.org/10.3390/ijms23105489.
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Besides the loss of muscle mass and strength, increased intermuscular adipose tissue (IMAT) is now a well-recognized consequence of muscle deconditioning as experienced in prolonged microgravity. IMAT content may alter the muscle stem cell microenvironment. We hypothesized that extracellular matrix structure alterations and microenvironment remodeling induced by fast and severe muscle disuse could modulate fibro-adipogenic progenitor fate and behavior. We used the dry immersion (DI) model that rapidly leads to severe muscle deconditioning due to drastic hypoactivity. We randomly assigned healthy volunteers (n = 18 men) to the control group (only DI, n = 9; age = 33.8 ± 4) or to the DI + thigh cuff group (n = 9; age = 33.4 ± 7). Participants remained immersed in the supine position in a thermo-neutral water bath for 5 days. We collected vastus lateralis biopsies before (baseline) and after DI. 5 days of DI are sufficient to reduce muscle mass significantly, as indicated by the decreased myofiber cross-sectional area in vastus lateralis samples (−18% vs. baseline, p < 0.05). Early and late adipogenic differentiation transcription factors protein levels were upregulated. Platelet-derived growth Factors alpha (PDGFR⍺) protein level and PDGFR⍺-positive cells were increased after 5 days of DI. Extracellular matrix structure was prone to remodeling with an altered ECM composition with 4 major collagens, fibronectin, and Connective Tissue Growth Factor mRNA decreases (p < 0.001 vs. baseline). Wearing thigh cuffs did not have any preventive effect on the measured variable. Our results show that altered extracellular matrix structure and signaling pathways occur early during DI, a severe muscle wasting model, favoring fibro-adipogenic progenitor differentiation into adipocytes.
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Fu, Xing. "209 A Single-Cell Atlas of Bovine Skeletal Muscle Tissue Reveals Mechanisms Underlying Differences in Quality between Wagyu and Brahman Beef." Journal of Animal Science 100, Supplement_3 (2022): 190–91. http://dx.doi.org/10.1093/jas/skac247.350.
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Abstract Wagyu cattle are renowned for their premium beef characterized by abundant intramuscular fat (IMF). In contrast, Brahman, a popular breed in the southern coastal area of the US, generally produces tough meat with scarce IMF. However, the mechanisms underlying the differential meat quality between the 2 breeds are still largely unknown. Here, using single-cell RNAseq (scRNAseq), we report a single-cell atlas of bovine skeletal muscle tissue. Multiple fibro/adipogenic progenitor (FAP) subpopulations were identified, including an endomysial adipogenic subpopulation and a perimysial fibrogenic subpopulation. Further analysis comparing individual FAP subpopulations between Wagyu and Brahman identified stronger expression of pro-adipogenic genes in Wagyu adipogenic FAP subpopulation and higher expression of pro-fibrogenic genes in Brahman fibrogenic FAP subpopulation. Overexpression of CFD, a gene upregulated in Wagyu adipogenic FAPs, enhanced the adipogenic efficiency of FAPs. Moreover, the expression of CFD in FAPs was positively correlated with the IMF content. Interestingly, the expression of CFD was not identified in FAPs of mouse models of intramuscular adipogenesis, suggesting that CFD is a cattle-specific regulator of IMF formation. Cell-cell communication analysis reveals significant differences between CFD+ FAPs and CFD- FAPs in their interactions with other cell types, further suggesting an important role of CFD+ FAPs in bovine skeletal muscle growth and development.
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Sun, Liping, Yonghui Jin, Megumi Nishio, et al. "Oxidative phosphorylation is a pivotal therapeutic target of fibrodysplasia ossificans progressiva." Life Science Alliance 7, no. 5 (2024): e202302219. http://dx.doi.org/10.26508/lsa.202302219.
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Heterotopic ossification (HO) is a non-physiological bone formation where soft tissue progenitor cells differentiate into chondrogenic cells. In fibrodysplasia ossificans progressiva (FOP), a rare genetic disease characterized by progressive and systemic HO, the Activin A/mutated ACVR1/mTORC1 cascade induces HO in progenitors in muscle tissues. The relevant biological processes aberrantly regulated by activated mTORC1 remain unclear, however. RNA-sequencing analyses revealed the enrichment of genes involved in oxidative phosphorylation (OXPHOS) during Activin A–induced chondrogenesis of mesenchymal stem cells derived from FOP patient–specific induced pluripotent stem cells. Functional analyses showed a metabolic transition from glycolysis to OXPHOS during chondrogenesis, along with increased mitochondrial biogenesis. mTORC1 inhibition by rapamycin suppressed OXPHOS, whereas OXPHOS inhibitor IACS-010759 inhibited cartilage matrix formation in vitro, indicating that OXPHOS is principally involved in mTORC1-induced chondrogenesis. Furthermore, IACS-010759 inhibited the muscle injury–induced enrichment of fibro/adipogenic progenitor genes and HO in transgenic mice carrying the mutated human ACVR1. These data indicated that OXPHOS is a critical downstream mediator of mTORC1 signaling in chondrogenesis and therefore is a potential FOP therapeutic target.
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Li, X., X. Fu, G. Yang, and M. Du. "Review: Enhancing intramuscular fat development via targeting fibro-adipogenic progenitor cells in meat animals." Animal 14, no. 2 (2020): 312–21. http://dx.doi.org/10.1017/s175173111900209x.
Full textDissertations / Theses on the topic "Fibro-adipogenic progenitor"
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Moratal, Claudine. "Les progéniteurs fibro-adipogéniques des muscles squelettiques humains sains et dystrophiques : caractérisation et interactions avec les progéniteurs myogéniques et les macrophages." Thesis, Université Côte d'Azur (ComUE), 2016. http://www.theses.fr/2016AZUR4128/document.
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La régénération musculaire implique des interactions fonctionnelles entre différents types de cellules mononucléées. Parmi elles, citons les progéniteurs myogéniques (MPs), qui fusionnent pour générer de nouvelles myofibres en réponse à une blessure, et les cellules immunitaires qui envahissent les muscles endommagés. Des dépôts transitoires fibrotiques et d’adipocytes sont observés dans les muscles en régénération qui cependant persistent dans la dystrophie musculaire de Duchenne (DMD) et au cours du vieillissement. Nous avons démontré que les progéniteurs fibro-adipogéniques (FAPs) exprimant le marqueur de surface PDGFRα, contribueraient au développement des dépôts non myogéniques dans les muscles sains. En effet, ces progéniteurs se différencient en adipocytes blancs fonctionnels, bien qu’étant insensibles à l’insuline, et génèrent des myofibroblastes. Quant à la fibrose des muscles DMD, elle se formerait à partir de la différenciation à la fois des MPs et des FAPs. Dans les muscles sains, les FAPs stimulent la myogenèse des MPs au cours de la régénération, alors que les myotubes et les macrophages pro-inflammatoires inhibent l’adipogenèse et la fibrogenèse des FAPs. Pour les progéniteurs âgés ou dystrophiques, les interactions cellulaires entre les FAPs et les MPs sont perturbées. De manière intéressante, la régulation des FAPs DMD ou âgés peut être restaurée en remplaçant les MPs DMD ou âgés par des MPs jeunes et sains. Nos résultats montrent que les muscles humains contiennent des progéniteurs fibro-adipogéniques qui jouent un rôle central dans la régulation de l’homéostasie musculaire en interagissant avec les progéniteurs myogéniques et les macrophages<br>Muscle regeneration involves functional interactions between different types of mononuclear cells including myogenic progenitors (MPs) and macrophages. Following injury, damaged muscles are invaded by immune cells and MPs fuse to generate new myofibres. Transient fibrotic and adipocyte deposits are observed in regenerating muscles, which however persist in Duchenne muscular dystrophy (DMD) and during aging. We demonstrated that fibro-adipogenic progenitors (FAPs) expressing the PDGFRα surface marker would contribute to the development of non-myogenic deposits in healthy muscles. Indeed, these progenitors differentiate into functional white adipocytes that have the feature to be insulino-resistant, and give rise to myofibroblastes. Intramuscular fibrosis in DMD patients could be formed from both FAPs and MPs differentiation. In healthy muscles, FAPs stimulate myogenesis of MPs during regeneration, while myotubes and pro-inflammatory macrophages inhibit the adipogenesis and fibrogenesis of FAPs. Cellular interactions between FAPs and MPs are disrupted for DMD or aged progenitors. Interestingly, they are restored if aged or DMD FAPs are replaced by healthy and young MPs. Our results show that the human muscles contain fibro-adipogenic progenitors that play a crucial role in the control of muscle homeostasis by interacting with myogenic progenitors and macrophages
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Moratal, Claudine. "Les progéniteurs fibro-adipogéniques des muscles squelettiques humains sains et dystrophiques : caractérisation et interactions avec les progéniteurs myogéniques et les macrophages." Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2016. http://www.theses.fr/2016AZUR4128.
Full textAbstract:
La régénération musculaire implique des interactions fonctionnelles entre différents types de cellules mononucléées. Parmi elles, citons les progéniteurs myogéniques (MPs), qui fusionnent pour générer de nouvelles myofibres en réponse à une blessure, et les cellules immunitaires qui envahissent les muscles endommagés. Des dépôts transitoires fibrotiques et d’adipocytes sont observés dans les muscles en régénération qui cependant persistent dans la dystrophie musculaire de Duchenne (DMD) et au cours du vieillissement. Nous avons démontré que les progéniteurs fibro-adipogéniques (FAPs) exprimant le marqueur de surface PDGFRα, contribueraient au développement des dépôts non myogéniques dans les muscles sains. En effet, ces progéniteurs se différencient en adipocytes blancs fonctionnels, bien qu’étant insensibles à l’insuline, et génèrent des myofibroblastes. Quant à la fibrose des muscles DMD, elle se formerait à partir de la différenciation à la fois des MPs et des FAPs. Dans les muscles sains, les FAPs stimulent la myogenèse des MPs au cours de la régénération, alors que les myotubes et les macrophages pro-inflammatoires inhibent l’adipogenèse et la fibrogenèse des FAPs. Pour les progéniteurs âgés ou dystrophiques, les interactions cellulaires entre les FAPs et les MPs sont perturbées. De manière intéressante, la régulation des FAPs DMD ou âgés peut être restaurée en remplaçant les MPs DMD ou âgés par des MPs jeunes et sains. Nos résultats montrent que les muscles humains contiennent des progéniteurs fibro-adipogéniques qui jouent un rôle central dans la régulation de l’homéostasie musculaire en interagissant avec les progéniteurs myogéniques et les macrophages<br>Muscle regeneration involves functional interactions between different types of mononuclear cells including myogenic progenitors (MPs) and macrophages. Following injury, damaged muscles are invaded by immune cells and MPs fuse to generate new myofibres. Transient fibrotic and adipocyte deposits are observed in regenerating muscles, which however persist in Duchenne muscular dystrophy (DMD) and during aging. We demonstrated that fibro-adipogenic progenitors (FAPs) expressing the PDGFRα surface marker would contribute to the development of non-myogenic deposits in healthy muscles. Indeed, these progenitors differentiate into functional white adipocytes that have the feature to be insulino-resistant, and give rise to myofibroblastes. Intramuscular fibrosis in DMD patients could be formed from both FAPs and MPs differentiation. In healthy muscles, FAPs stimulate myogenesis of MPs during regeneration, while myotubes and pro-inflammatory macrophages inhibit the adipogenesis and fibrogenesis of FAPs. Cellular interactions between FAPs and MPs are disrupted for DMD or aged progenitors. Interestingly, they are restored if aged or DMD FAPs are replaced by healthy and young MPs. Our results show that the human muscles contain fibro-adipogenic progenitors that play a crucial role in the control of muscle homeostasis by interacting with myogenic progenitors and macrophages
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Pagano, Allan. "Déconditionnement et régénération du muscle strié squelettique : rôle du niveau d’activité contractile sur le développement d’infiltrations graisseuses." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONT4004/document.
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Le muscle strié squelettique est un tissu fascinant qui permet d’assurer les fonctions essentielles à notre existence : se mouvoir, maintenir sa posture, se nourrir, communiquer ou tout simplement respirer. De nombreuses situations, engendrant principalement une hypoactivité, peuvent provoquer un déconditionnement musculaire caractérisé par une perte de masse et de force ainsi qu’un développement d’infiltrations graisseuses (IMAT), altérant ainsi la fonction musculaire. Le développement d’IMAT est également observé lorsque les processus de régénération musculaire sont altérés. Les fibro-adipogenic progenitors (FAPs) représentent la population de cellules souches principalement impliquée dans le développement d’IMAT. L’interaction entre FAPs et cellules satellites/immunitaires semble être un trio indispensable pour une régénération optimale, sans développement d’IMAT. Au regard de la littérature scientifique, une modulation du niveau d’activité contractile permet de faire varier le niveau d’expression de nombreuses cytokines impliquées dans la modulation des FAPs et donc dans l’apparition d’IMAT. Nos travaux ont contribué à l’accroissement des connaissances scientifiques relatives à la thématique des infiltrations graisseuses et à leurs exacerbations dans des situations d’hypoactivité ou de régénération musculaire. Nous avons montré que 3 jours d’hypoactivité chez l’homme, induite par le modèle novateur de dry immersion, suffisent à augmenter le contenu musculaire en IMAT. Dans un contexte de régénération musculaire, induite par le modèle glycérol chez la souris, nous avons démontré une inhibition de l’apparition des IMAT en diminuant les contraintes mécaniques appliquées au muscle lésé. Nous avons également précisé le rôle de l’axe TNFα/TGF-β1, et donc celui des processus inflammatoires nécessaires dans l’apoptose des FAPs afin de limiter le développement des IMAT dans ce modèle. Ces trois études ouvrent de nombreuses perspectives, afin i) de préciser le rôle des IMAT dans la dysfonction musculaire, ii) de définir les mécanismes de régulation qui contrôlent le développement et l’accumulation d’IMAT<br>Skeletal muscle is a fascinating tissue that ensures core functions: moving, maintaining postures, feeding, communicating or just breathing. Many situations, associated with hypoactivity, are able to involve muscle deconditioning defined by a loss of mass and strength, as well as fat infiltration development (IMAT), altogether impairing muscle function. IMAT development occurs also with disrupted regeneration processes. Fibro-adipogenic progenitors (FAPs) appear as the main stem cell population involved in IMAT development. The interaction between FAPs and satellite/immune cells seems to be a crucial trio for an efficient regeneration, without IMAT development. According to the literature, the degree of contractile activity is able to affect the expression levels of different cytokines involved in FAPs fate, and therefore in IMAT accumulation. Our work contributed to increase scientific knowledge on muscle fatty infiltrations and their exacerbations in hypoactivity or regeneration situations. We showed that 3 days of hypoactivity in human, induced by the innovative model of dry immersion, are sufficient to promote an increase in IMAT content. In a context of muscle regeneration, induced by the mouse glycerol model, we highlighted an almost complete inhibition of IMAT accumulation by decreasing mechanical constraints applied to the injured muscle. We also investigated the role of the TNFα/TGF-β1 axis, and therefore the potential role of the inflammatory stage in FAPs apoptosis and inhibition of IMAT development. Our work open up new prospects 1°) clarifying the role of IMAT in muscle dysfunction, and 2°) defining the underlying mechanisms controlling IMAT development and accumulation
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Muraine, Laura. "Acteurs cellulaires et moléculaires de la fibrose dans les pathologies musculaires humaines." Electronic Thesis or Diss., Sorbonne université, 2023. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2023SORUS192.pdf.
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Les pathologies musculaires ou myopathies constituent un groupe hétérogène de maladies caractérisées par une faiblesse et une dégénérescence progressive du muscle squelettique. Parmi elles, la dystrophie musculaire de Duchenne (DMD) est une myopathie sévère d’origine génétique qui touche la plupart des muscles squelettiques et le muscle cardiaque dès le plus jeune âge, alors que la dystrophie musculaire oculopharyngée (OPMD), d’origine génétique, et la myosite à inclusions (IBM) d’origine acquise sont des pathologies qui affectent des muscles spécifiques, notamment les muscles du pharynx, et où les symptômes apparaissent plus tardivement. Dans toutes ces pathologies, les muscles atteints présentent une importante fibrose : une accumulation excessive de matrice extracellulaire (MEC), qui altère l’architecture, la fonction musculaire ainsi que l’efficacité de thérapies innovantes. A ce jour, plusieurs acteurs cellulaires ont été décrits comme impliqués dans l’établissement et le maintien de la fibrose musculaire : les progéniteurs fibro-adipogéniques (FAPs), les macrophages ou encore les cellules satellites (cellules souches du muscle). Cependant, les mécanismes impliqués restent méconnus et peu d’études ont caractérisé, dans le muscle squelettique humain, le rôle de la MEC et des FAPs qui la sécrètent. Dans ce contexte, nous avons analysé par une approche protéomique, les acteurs moléculaires de la fibrose dans ces trois myopathies : la DMD, l’OPMD et l’IBM et mis en évidence des variations de composition de la MEC spécifiques à chaque pathologie. En isolant les différents types cellulaires à partir de biopsies de muscles humains contrôles ou fibrotiques, nous avons étudié le dialogue entre les FAPs et les cellules musculaires. Nous avons ainsi mis en évidence un profil spécifique des FAPs issus de muscles fibrotiques, caractérisé par une prolifération et une sécrétion accrue, ainsi qu’une influence négative des FAPs sur la différenciation musculaire. Nous avons identifié l'endothéline comme un des acteurs impliqués dans ce cross-talk altéré, et donc comme une cible thérapeutique potentielle. Ces résultats mettent en évidence le rôle prépondérant de l’environnement cellulaire et moléculaire sur le fonctionnement musculaire et soulignent la nécessité d’interactions finement régulées entre les différents acteurs cellulaires, au sein du muscle. L’ensemble de ces travaux participent à améliorer notre compréhension des mécanismes impliqués dans la mise en place et le maintien de la fibrose musculaire humaine dans le but de développer des thérapies anti-fibrotiques efficaces<br>Muscular disorders, or myopathies are a heterogeneous group of diseases characterized by weakness and/or progressive degeneration of muscle tissue with a wide clinical presentation and severity. Duchenne muscular dystrophy (DMD) is a severe genetic myopathy that affects all muscles from childhood, while genetic oculopharyngeal muscular dystrophy (OPMD) and acquired inclusion body myositis (IBM) are pathologies that affect fewer muscles, including pharyngeal muscles, and where the symptoms appear after 50 years. Muscles affected in these pathologies all develop fibrosis: an excessive accumulation of extracellular matrix (ECM) which alters muscle architecture and function, as well as the potential of innovative therapeutic strategies. Several cellular actors are known to take part in the establishment and the maintenance of fibrosis: fibro-adipogenic progenitors (FAPs), macrophages as well as satellite cells (muscle stem cells). However, the mechanisms involved in this process remain elusive and few studies have characterized the involvement of the ECM and the FAPs in human skeletal muscle. In this context, we compared, by a proteomic analysis, the molecular actors of fibrosis in these three myopathies: DMD, OPMD and IBM, and highlighted disease specific variations in ECM composition. After isolation of human cells from control and fibrotic biopsy samples, we studied the cross-talk between FAPs and muscle cells. We demonstrated a specific profile of FAPs from fibrotic muscles, characterized by an increased proliferation and secretion, and a negative effect of those cells on muscle differentiation. We identified endothelin as one of the actors involved in the altered cross-talk, and thus a potential therapeutic target. Those results highlight the significant role of the cellular and molecular environment on muscle function and underline the need of well-orchestrated interactions between cellular actors within the muscle. This work improves our understanding of the mechanisms involved in the initiation and maintenance of human muscle fibrosis and provides clues for developing effective anti-fibrotic therapies
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Guerra, Badell Joana 1986. "Cooperative interactions of stem and niche cells during skeletal muscle regeneration: role of IL-6 signaling." Doctoral thesis, Universitat Pompeu Fabra, 2016. http://hdl.handle.net/10803/482050.
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Adult skeletal muscle has a remarkable capacity of self-repairing after damage. The cellular communication processes and mediator molecules in the regenerative microenvironment that control muscle stem cell functions are poorly characterized. Muscle resident fibro/adipogenic progenitors (FAPs) are responsible of the fibrotic and adipose degeneration of muscle in pathological situations. In contrast with this function, here we demonstrate that blood-infiltrating neutrophils cooperate with FAPs to promote muscle regeneration after injury. By cell-type specific gene deletion and transplantation experiments, here we show the requirement of the soluble form of interleukin 6 (IL-6) receptor released by neutrophils and FAP-derived IL-6 to activate IL-6 trans-signaling for efficient muscle stem cell proliferative and regenerative functions. Exploitation of this physiological mechanism may be of therapeutic importance in pathologies coursing with poor regeneration of skeletal muscle.<br>El múscul esquelètic adult té una notable capacitat d’autoregenerar-se després d’un dany. Els processos de comunicació cel·lular i les molècules mediadores que controlen les funcions de les cèl·lules mare musculars en el microambient regeneratiu, no han estat caracteritzats detalladament. Els progenitors fibro/adipogènics (FAPs) residents en el múscul esquelètic són responsables de la degeneració fibro/adiposa que pateix el teixit muscular en situacions patològiques. Contràriament a aquesta funció, aquest treball demostra que els FAPs cooperen amb els neutròfils provinents de la sang i que infiltren el teixit danyat, per expandir el nombre de cèl·lules mare musculars després d’una lesió. Mitjançant la supressió de l’expressió de gens específicament en diferents tipus cel·lulars i experiments de trasplantament, demostrem el requeriment de la interleucina 6 (IL-6), produïda de forma local i transitòria pels FAPs, que actua conjuntament amb la forma soluble del receptor de IL-6 (sIL-6Rα), alliberat pels neutròfils, per activar la trans-senyalització per IL-6 i així promoure la regeneració. L'explotació d'aquest mecanisme fisiològic pot tenir una importància terapèutica en patologies amb una deficient regeneració muscular.
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Cazin, Coralie. "Dissecting the impact of cellular senescence on muscle regeneration." Electronic Thesis or Diss., Sorbonne université, 2020. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2020SORUS070.pdf.
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La régénération tissulaire est un processus de remplacement des cellules perdues ou endommagées lors d'une blessure. La sénescence cellulaire est une réponse physiologique au stress caractérisée par un arrêt du cycle cellulaire stable. Mon doctorat vise à étudier la sénescence in vivo lors de la régénération musculaire, y compris son identité, ses fonctions et sa dynamique. Nous avons précédemment démontré que la sénescence induite par blessure favorise la reprogrammation dans le muscle squelettique. Mon projet vise à étudier la biologie de la sénescence lors de la régénération musculaire de manière systémique. Premièrement, j'ai montré que la sénescence atteignait son maximum au 3ème jour après la blessure et se terminait au 15ème jour après la blessure. Ensuite, j'ai trouvé que les FAPs (Fibro-Adipogenic Progenitors) sont les principales cellules qui deviennent sénescentes. Par ailleurs, les FAPs sénescents améliorent peut-être la myogenèse in vitro de manière paracrine. P57 est le principal inhibiteur de CDK qui permet l’induction de la sénescence associée aux FAPs. En effet, il y a une réduction significative de la sénescence induite par blessure chez les souris P57KO. Enfin, nous avons trouvé que Mcl-1 est surexprimé dans les FAPs sénescents, ce qui suggère l'utilisation potentielle d’inhibiteurs de MCL-1 comme drogues sénolytiques. Dans l’ensemble, mon doctorat montre que les FAPs sont sénescents lors d'une lésion musculaire, via P57 et pourraient être important pour la régénération musculaire en favorisant la myogenèse. Ces découvertes soutiennent fortement le rôle bénéfique de la sénescence lors de la régénération musculaire<br>Tissue regeneration is a process of replacing lost or damaged cells upon injury. Cellular senescence is a physiological response to stress characterized by a stable cell cycle arrest and is associated with various biological and pathological processes. My Ph.D. project aims to investigate in vivo senescence during muscle regeneration, including its identities, functions, and dynamics. It has been demonstrated that cellular senescence could facilitate optimal wound healing. We previously demonstrated that injury-induced senescence promotes reprogramming in the skeletal muscle, notably through IL-6 (Chiche et al., 2017). Firstly, I showed that senescence was peaking at day 3 post-injury and terminated by day 15 post injury. Then, I found that FAPs is the primary cell type that becomes senescent by RNA sequencing (both bulk population and single-cell). Besides, senescent FAPs enhance myogenesis in vitro in a paracrine manner. Of note, P57 is the major CKI which mediates the FAPs-associated senescence. Importantly, there is a significant reduction of the injury-induced senescence in the P57 null mice. Lastly, we found Mcl-1 is overexpressed in the senescent FAPs, suggesting the potential usage of MCL-1 inhibitors as senolytic drugs.Taken together, my ph.D show that FAPs are senescent upon muscle injury, which is P57-dependent and might be important to muscle regeneration by enhancing myogenesis. These findings strongly support a beneficial role of senescence during muscle regeneration, which has direct implications in muscular degenerative diseases and muscle aging
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Dal, Cin Julian. "Analyse tissulaire des myopathies inflammatoires idiopathiques et induites par immune-checkpoint-inhibitor : apport des nouvelles approches transcriptomiques." Electronic Thesis or Diss., Sorbonne université, 2023. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2023SORUS151.pdf.
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Les myosites forment un groupe hétérogène de pathologies auto-immunes partageant une atteinte musculaire des patients. Les myosites sont séparées en 5 sous-entités : les dermatomyosites (DM), les syndromes des anti-synthétases (ASyS), les myosites à inclusions (IBM), les myopathies nécrosantes auto-immunes (IMNM) et les myosites induites par inhibiteur de point de contrôle immunitaire (ICI). Les mécanismes physiopathologiques, le phénotype clinique et le pronostic de chaque sous-entité sont différents. Parmi les myosites, ce travail s’est concentré sur les IMNM et les myosites induites par ICI, leur pronostic étant le plus sombre. Des études transcriptomiques à haute résolution, spatiale ainsi qu’en cellule unique ont permis d’étudier le tissu musculaire des patients atteints de ces myosites. Dans les myosites induites par ICI, ces études ont confirmé la cytotoxicité de lymphocytes T CD8 et leur rôle central, principalement celui des populations de lymphocytes T résidents mémoires identifiés dans le muscle ainsi que des macrophages. Nous proposons un modèle pathogénique basé sur la réaction de lymphocytes T résidents mémoires aux traitements ICI. Dans les IMNM, des sous-groupes de macrophages ont été identifiés composés respectivement des macrophages pro-inflammatoires, anti-inflammatoires et de macrophages accompagnés de progéniteurs fibro-adipeux (FAP). Nous proposons que la nécrose stimulerait les macrophages et induirait leur recrutement ce qui permettrait la prolifération des FAP à l’origine de la fibrose exacerbée des patients. La compréhension de ces mécanismes parmi d’autres permet d’envisager de nouvelles cibles thérapeutiques et d’améliorer le pronostic des patients<br>Myositis are a heterogeneous group of autoimmune pathologies characterized by muscle damage in patients. Myositis are separated into 5 subgroups: dermatomyositis (DM), anti-synthetase syndromes (ASyS), inclusion body myositis (IBM), autoimmune necrotizing myopathies (IMNM) and immune-checkpoint inhibitor (ICI)-induced myositis. The pathophysiological mechanisms, clinical phenotype and prognosis of each subgroup are different. Among myositis, this work focused on IMNM and ICI-induced myositis, which have the poorest prognosis. High-resolution, spatial and single-cell transcriptomic studies have made it possible to study the muscle tissue of patients with these myositis. In ICI-induced myositis, these studies have confirmed the cytotoxicity of CD8 T cells and their central role, mainly of a population of resident memory T cells identified in the muscle, as well as macrophages. We propose a pathogenic model based on the reaction of resident memory T cells to ICI treatments. In IMNM, subgroups of macrophages have been identified composed respectively of pro-inflammatory macrophages, anti-inflammatory macrophages, and macrophages close to fibro-adipogenic progenitors (FAP). We propose that necrosis can stimulate macrophages and induce their recruitment, which would allow the proliferation of FAPs at the origin of exacerbated fibrosis in patients. Understanding mechanisms among others makes it possible to consider new therapeutic targets and improve patient prognosis
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BIFERALI, BEATRICE. "H3K9 methylation controls Fibro-Adipogenic Progenitors identity and skeletal muscle repair." Doctoral thesis, 2020. http://hdl.handle.net/11573/1380567.
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Fibro-Adipogenic Progenitors (FAPs) are crucial regulators of muscle homeostasis as they possess the intrinsic ability to either support muscle regeneration or to contribute to fibro-adipogenic degeneration of dystrophic muscles. Therefore, the elucidation of the molecular mechanisms controlling their phenotypical plasticity holds therapeutic potential. Here we provide evidence that FAPs are particularly enriched in histone H3 lysine K9 methyltransferases (H3K9 KMTs), G9a, GLP and Prdm16. Our data indicate that H3K9 KMTs safeguard FAPs identity by repressing alternative transcriptional programs through deposition of H3K9 di- methylation (H3K9me2). Specifically, we show that Prdm16 controls G9a/GLP-mediated deposition of H3K9me2 at muscle- specific loci. Of note, we found Prdm16, G9a and GLP particularly enriched at the nuclear lamina (NL) of FAPs, suggesting they organize heterochromatin at the nuclear periphery to maintain the stable repression of genes encoding alternative developmental regulators. Accordingly, pharmacological inhibition or RNAi- mediated knock-down (KD) of H3K9 KMTs de-repress master myogenic genes in FAPs and induce the muscle differentiation program. Together, our findings reveal a FAPs-specific epigenetic axis important to control their identity. These findings are important especially for the possible therapeutic application to conceive strategies aimed to reprogram FAPs fate in vivo to prevent degeneration of diseased muscles.
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TUCCIARONE, LUCA. "Epigenetic and transcriptomic profiling of fibro adipogenic progenitors during Duchenne muscular dystrophy progression and histone deacetylase inhibitors treatment." Doctoral thesis, 2020. http://hdl.handle.net/11573/1342755.
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Duchenne Muscular Dystrophy (DMD) is a lethal disease caused by mutations in the Dystrophin gene. DMD is characterized by continuous cycles of muscle contraction/degeneration, leading to muscular tissue replacement by fibrotic and fat infiltrations deposed by the fibro-adipogenic progenitors (FAPs). Although there is currently no cure for DMD, the Histone Deacetylase Inhibitors (HDACi) represent the first generation of epigenetic drugs used to counteract DMD progression. Our lab has identified a regulatory network targeted by HDACi to repress FAPs differentiation into fibro-adipogenic cells, while activating a latent pro-myogenic phenotype (Saccone et al. 2014). However, HDACi pharmacological efficacy is restricted at early stage of DMD (Mozzetta et al. 2013). The mechanism during dystrophic FAPs aging that confers resistance to HDACi treatment is still unknown. To address this issue, we performed ChIP-seq for H3K9/14ac and H3K27ac in FAPs from early and late stage dystrophic mice, treated or not with HDACi. Coupling ChIP-seq with RNA-seq we identified differentially acetylated regions responsible of gene expression changes and unveiled the stage-specific epi-signature of both HDACi efficacy and resistance. This work paves the way to future diagnostic and therapeutic perspective for extending the efficacy of HDACi for the treatment of DMD.
Book chapters on the topic "Fibro-adipogenic progenitor"
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Low, Marcela, Christine Eisner, and Fabio Rossi. "Fibro/Adipogenic Progenitors (FAPs): Isolation by FACS and Culture." In Methods in Molecular Biology. Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4939-6771-1_9.
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Judson, Robert N., Marcela Low, Christine Eisner, and Fabio M. Rossi. "Isolation, Culture, and Differentiation of Fibro/Adipogenic Progenitors (FAPs) from Skeletal Muscle." In Methods in Molecular Biology. Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4939-7283-8_7.
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Tucciarone, Luca, Usue Etxaniz, Martina Sandoná, Silvia Consalvi, Pier Lorenzo Puri, and Valentina Saccone. "Advanced Methods to Study the Cross Talk Between Fibro-Adipogenic Progenitors and Muscle Stem Cells." In Methods in Molecular Biology. Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4939-7374-3_17.
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Elhussieny, Ahmed, Ken’ichiro Nogami, Fusako Sakai-Takemura, et al. "Mesenchymal Stem Cells for Regenerative Medicine for Duchenne Muscular Dystrophy." In Muscular Dystrophy - Research Updates and Therapeutic Strategies. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.92824.
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Mesenchymal stem cells (MSCs) are multipotent stem cells that can be isolated from both foetal and adult tissues. Several groups demonstrated that transplantation of MSCs promoted the regeneration of skeletal muscle and ameliorated muscular dystrophy in animal models. Mesenchymal stem cells in skeletal muscle, also known as fibro-adipogenic progenitors (FAPs), are essential for the maintenance of skeletal muscle. Importantly, they contribute to fibrosis and fat accumulation in dystrophic muscle. Therefore, MSCs in muscle are a pharmacological target for the treatment of muscular dystrophies. In this chapter, we briefly update the knowledge on mesenchymal stem/progenitor cells and discuss their therapeutic potential as a regenerative medicine treatment of Duchenne muscular dystrophy.
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Srpčič, Anja, Felicita Urzi, Sanja Markez, et al. "Skeletal Muscle Involvement in Systemic Sclerosis." In Systemic Sclerosis - Recent Advances and New Perspectives [Working Title]. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.1003687.
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Systemic sclerosis (SSc) is a systemic autoimmune connective tissue disease with great clinical and pathogenetic heterogeneity. Although skin is the most visible organ affected, skeletal muscles are affected in up to 96% of SSc patients and this is associated with a worse clinical outcome including increased mortality. Muscle involvement varies from patients experiencing myalgias, fibrosing myopathy to overlaps of SSc and myositis, a condition referred to as scleromyositis. In SSc muscle biopsies, muscular fibrosis, inflammation, microangiopathy and atrophy are observed, which is consistent with most prominent SSc pathophysiologic processes. The damage and fibrosis of the muscle tissue and the reduced ability of the body to build and repair muscle lead to a loss of muscle mass and strength. Studies show that patients with SSc have a higher prevalence of myopenia than the general population, but the exact cause is not yet fully understood. Partially, this phenomenon could be attributed to the disrupted activity of fibro-adipogenic progenitors, driven by alterations in the skeletal muscle microenvironment of SSc patients. These changes are also reflected in shifts in myokine secretion.