Two post-doctoral positions in skeletal muscle stem cell environment
Profile 1 – exploration of the role of extracellular matrix in skeletal muscle biology (PI: Dr. B Chazaud). The candidate must have an experience working in the biology and biochemistry of extracellular matrix. A background in skeletal muscle biology is a plus, but not mandatory.
Profile 2 – exploration of the role of myofiber contraction on skeletal muscle environment (PI: Dr. R Mounier). The candidate must have an experience working in the biology and physiology of skeletal muscle, with a reference to in vitro/ex vivo muscle cell contraction.More info here
Adult stem cells are involved in the maintenance and repair of many tissues throughout life. Stem cells play particularly important roles in skeletal muscle, which shows high plasticity and regenerative properties to keep constant physiological parameters (homeostasis). Healthy skeletal muscle mobilizes tissue-associated endogenous stem cells, mainly satellite cells, to repair damaged myofibers. Muscle stem cell sustained regeneration is crucial for muscle homeostasis, as well as mechanisms of self-renewal that maintain their pool constant.
A key issue we address is the tissue environment in which muscle stem cells are activated and process adult myogenesis. This micro-environment plays important roles in the behavior of muscle stem cells and myogenic cells, although the mechanisms are still poorly known. Several cell types in the vicinity of stem cells communicate with each other to correctly drive regeneration. We explore the roles of immune cells (inflammation), endothelial and peri-endothelial cells (angiogenesis) and interstitial cells (fibrosis) on myogenic cell fate in healthy regenerating muscle and in various pathophysiological contexts (muscular dystrophies, cachexia). Indeed, muscle pathologies are characterized by alterations in the micro-environment of muscle cells, such as the presence of chronic inflammation or fibrosis, which are detrimental for tissue regeneration and homeostasis.
Muscle stem cell neighborhood (B. Chazaud and G. Mouchiroud)
Skeletal muscle regeneration is associated with the presence of macrophages. Two main inflammatory types of macrophages are present during skeletal muscle regeneration. Soon after injury, inflammatory monocytes enter into the damaged muscle and these inflammatory macrophages stimulate the proliferation of muscle stem cells. Later, they switch their phenotype into anti-inflammatory macrophages that sustain myogenic differentiation and myofiber growth. Macrophages can be considered as a stromal support for myogenic cells that helps the sequential steps of skeletal muscle regeneration. Our research focuses on the molecular mechanisms that regulate the inflammatory status and functions of macrophages during this process. We also study macrophage functions during myopathies, where they are associated with fibrosis.
We also investigate the interactions between muscle stem cells and vessel cells, since satellite cells are located close to capillaries in normal muscle. Endothelial cells and myogenic precursor cells interact to stimulate each other growth and differentiation. On the contrary peri-endothelial cells (smooth muscle cells) promote the self-renewal and maintain into quiescence of myogenic cells. We aim at understanding the molecular regulation of the coupling between angiogenesis and myogenesis during skeletal muscle regeneration, as well as identifying whether these interactions are altered – and how – in various myopathies.
Cell- and non-cell autonomous regulations of metabolism on muscle stem cell fate and skeletal muscle homeostasis (R. Mounier)
Mechanisms controlling muscle stem cell fate are poorly known and account for both cell autonomous and non-cell autonomous regulations. In this context, we investigate the role of metabolism on muscle stem cells by studying metabolic regulations of their fate, particularly the role of the energy sensor AMPK and the metabolic characteristics of muscle stem cells. The goal of our program is to determine the dynamic interactions between metabolism and muscle stem cell fate during muscle plasticity and return to homeostasis.
Neuromuscular electrical stimulation training to fight cachexia (J. Gondin)
Cachexia is a common consequence of many chronic diseases including sepsis and cancer. This loss of skeletal muscle mass ultimately results in increased morbidity and mortality. Moreover, treatments, sedation and/or prolonged unloading may further increase muscle deconditioning. On that basis, the development of countermeasures to prevent or attenuate the loss of skeletal muscle mass is of utmost importance for patients. Our aim is to investigate whether and to what extent NeuroMuscular Electrical Stimulation (NMES) is a promising therapy for increasing force production and promoting muscle growth in preclinical models of cachexia. The program aims at establishing rigorous protocols to exploit the benefit of NMES on muscle function and at identifying the cellular and molecular events underlying those beneficial effects.
- Macrophage-derived superoxide production and antioxidant response following skeletal muscle injury
Gitiaux C, Latroche C, Weiss-Gayet M, Rodero MP, Duffy D, Bader-Meunier B, Glorion C, Nusbaum P, Bodemer C, Mouchiroud G, Chelly J, Germain S, Desguerre I, Chazaud B. Arthritis Rheumatol. (2018) 70:134-145.
- Myogenic Progenitor Cells Exhibit Type I Interferon-Driven Proangiogenic Properties and Molecular Signature During Juvenile Dermatomyositis
Le Moal E, Juban G, Bernard AS, Varga T, Policar C, Chazaud B, Mounier R. Free Radic Biol Med. (2018) 20;120:33-40.
- Coupling between Myogenesis and Angiogenesis during Skeletal Muscle Regeneration Is Stimulated by Restorative Macrophages
Latroche C, Weiss-Gayet M, Muller L, Gitiaux C, Leblanc P, Liot S, Ben-Larbi S, Abou-Khalil R, Verger N, Bardot P, Magnan M, Chrétien F, Mounier R, Germain S, Chazaud B. Stem Cell Reports (2017) 9:2018-2033.
- AMPKa1-LDH pathway regulates muscle stem cell self-renewal by controlling metabolic homeostasis
Theret M, Gsaier L, Schaffer B, Juban G, Ben Larbi S, Weiss-Gayet M, Bultot L, Collodet C, Foretz M, Desplanches D, Sanz P, Zang Z, Yang L, Vial G, Viollet B, Sakamoto K, Brunet A, Chazaud B, Mounier R. EMBO J. (2017) 36:1946-1962.
- Macrophage PPARγ, a Lipid Activated Transcription Factor Controls the Growth Factor GDF3 and Skeletal Muscle Regeneration
Varga T, Mounier R, Patsalos A, Gogolák P, Peloquin M, Horvath A, Pap A, Daniel B, Nagy G, Pintye E, Póliska S, Cuvellier S, Larbi SB, Sansbury BE, Spite M, Brown CW, Chazaud B, Nagy L. Immunity (2016) 45:1038-1051.
- Highly Dynamic Transcriptional Signature of Distinct Macrophage Subsets during Sterile Inflammation, Resolution, and Tissue Repair
Varga T, Mounier R, Horvath A, Cuvellier S, Dumont F, Poliska S, Ardjoune H, Juban G, Nagy L, Chazaud B. J Immunol. (2016) 196:4771-4782.
- Myeloid HIFs are dispensable for resolution of inflammation during skeletal muscle regeneration
Gondin J, Theret M, Duhamel G, Pegan K, Mathieu JR, Peyssonnaux C, Cuvellier S, Latroche C, Chazaud B, Bendahan D, Mounier R. J Immunol. (2015) 194:3389-3399.
- AMPKalpha1 regulates macrophage skewing at the time of resolution of inflammation during skeletal muscle regeneration
Mounier R, Theret M, Arnold L, Cuvellier S, Bultot L, Goransson O, Sanz N, Ferry A, Sakamoto K, Foretz M, Viollet B, Chazaud B. Cell Metab. (2013) 18:251-264.
- Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration
Saclier M, Yacoub-Youssef H, Mackey AL, Arnold L, Ardjoune H, Magnan M, Sailhan F, Chelly J, Pavlath GK, Mounier R, Kjaer M, Chazaud B. Stem Cells (2013) 31:384-396.
- Tissue LyC6- macrophages are generated in the absence of circulating LyC6- monocytes and Nur77 in a model of muscle regeneration
Varga T, Mounier R, Gogolak P, Poliska S, Chazaud B, Nagy L. J Immunol. (2013) 191:5695-5701.
Faculté de Médecine
3ème étage, Aile A
8 Avenue Rockfeller
- Agence Nationale de Lutte contre le Dopage
- Agence Nationale de la Recherche
- Association Française contre les Myopathies
- Fondation pour la Recherche Médicale
- Ligue Contre le Cancer
- Université de Lyon - Université Claude Bernard Lyon 1