Nicolas Dumont

Nicolas Dumont
Université de Montréal | UdeM · Sainte-Justine University Hospital Center Research Center

PT, PhD

About

51
Publications
21,828
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2,899
Citations
Citations since 2017
22 Research Items
2412 Citations
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Publications

Publications (51)
Preprint
Full-text available
In skeletal muscle, muscle stem cells (MuSC) are the main cells responsible for regeneration upon injury. In diseased skeletal muscle, it would be therapeutically advantageous to replace defective MuSCs, or rejuvenate them with drugs to enhance their self-renewal and ensure longterm regenerative potential. One limitation of the replacement approach...
Article
Full-text available
Skeletal muscle possesses a high plasticity and a remarkable regenerative capacity that relies mainly on muscle stem cells. Molecular and cellular components of the muscle stem cell niche, such as immune cells, play key roles to coordinate muscle stem cell function and to orchestrate muscle regeneration. An abnormal infiltration of immune cells and...
Article
Full-text available
Skeletal muscle is populated with a reservoir of quiescent muscle stem cells (MuSCs), which regenerate the tissue after injury. Here, we show that the adhesion G-protein-coupled receptor Gpr116 is essential for long-term maintenance of the MuSC pool. Quiescent MuSCs express high levels of Gpr116, which is rapidly downregulated upon MuSC activation....
Article
Full-text available
A series of well-regulated cellular and molecular events result in the compartmentalization of the anterior foregut into the esophagus and trachea. Disruption of the compartmentalization process leads to esophageal atresia/tracheoesophageal fistula (EA/TEF). The cause of EA/TEF remains largely unknown. Therefore, to mimic the early development of t...
Preprint
Full-text available
Impaired skeletal muscle stem cell (MuSC) function has long been suspected to contribute to the pathogenesis of muscular dystrophy (MD). Here we describe that defects in the endothelial cell (EC) compartment of the perivascular stem cell niche in three different types of MD are associated with inefficient mobilization of MuSCs following tissue dama...
Preprint
Muscle weakness and atrophy are clinical hallmarks of myotonic dystrophy type 1 (DM1). Muscle stem cells, which contribute to skeletal muscle growth and repair, are also affected in this disease. However, the molecular mechanisms leading to this defective activity and the impact on the disease severity are still elusive. Here, we explored through a...
Article
Fate decisions in the embryo are controlled by a plethora of micro-environmental interactions in a three-dimensional niche. To investigate whether aspects of this microenvironmental complexity can be engineered to direct myogenic human-induced pluripotent stem cell (hiPSC) differentiation, we here screened murine cell types present in the developme...
Article
Front Cover: The cover image is based on the Research Article ERK3‐MK5 signaling regulates myogenic differentiation and muscle regeneration by promoting FoxO3 degradation by Sylvain Meloche et al., https://doi.org/10.1002/jcp.30695.
Preprint
A series of well-regulated cellular and molecular events result in the compartmentalization of the anterior foregut into the esophagus and trachea. Disruption of the compartmentalization process leads to esophageal atresia/tracheoesophageal fistula (EA/TEF). Therefore, the objective is to differentiate pluripotent stem cells (PSCs), namely, embryon...
Article
The physiological functions and downstream effectors of the atypical mitogen‐activated protein kinase extracellular signal‐regulated kinase 3 (ERK3) remain to be characterized. We recently reported that mice expressing catalytically‐inactive ERK3 (Mapk6KD/KD) exhibit a reduced postnatal growth rate as compared to control mice. Here, we show that ge...
Article
Muscular dystrophies are caused by genetic variants in genes encoding for proteins important for muscle structure or function, leading to a loss of muscle integrity and muscle wasting. To this day, no cure has been found for these diseases. Different therapeutic approaches are under intensive investigation. Cellular therapy has been extensively stu...
Article
Full-text available
Skeletal muscle possesses a remarkable regenerative capacity that relies on the activity of muscle stem cells, also known as satellite cells. The presence of non-myogenic cells also plays a key role in the coordination of skeletal muscle regeneration. Particularly, fibro-adipogenic progenitors (FAPs) emerged as master regulators of muscle stem cell...
Article
Full-text available
Individuals born preterm show reduced exercise capacity and increased risk for pulmonary and cardiovascular diseases, but the impact of preterm birth on skeletal muscle, an inherently critical part of cardiorespiratory fitness, remains unknown. We evaluated the impacts of preterm birth-related conditions on the development, growth, and function of...
Article
Full-text available
Lack of dystrophin causes muscle degeneration, which is exacerbated by chronic inflammation and reduced regenerative capacity of muscle stem cells in Duchenne Muscular Dystrophy (DMD). To date, glucocorticoids remain the gold standard for the treatment of DMD. These drugs are able to slow down the progression of the disease and increase lifespan by...
Preprint
The physiological functions and downstream effectors of the atypical mitogen-activated protein kinase ERK3 remain to be characterized. We recently reported that mice expressing catalytically-inactive ERK3 (Mapk6KD/KD) exhibit a reduced post-natal growth rate as compared to control mice. Here, we show that genetic inactivation of ERK3 impairs post-n...
Poster
Les nouveau-nés prématurés, qui représentent 7,7% des naissances au Québec, sont exposés à de hautes concentrations d’oxygène (O2), comparées à celles de la vie in utero, qui induisent un stress oxydatif et une inflammation systémique ayant des effets délétères sur des organes immatures. Considérant l’importance de l’hypoxie sur la maintenance et l...
Article
Full-text available
Muscle regeneration is a closely regulated process that involves a variety of cell types such as satellite cells, myofibers, fibroadipogenic progenitors, endothelial cells, and inflammatory cells. Among these different cell types, macrophages emerged as a central actor coordinating the different cellular interactions and biological processes. Parti...
Article
Full-text available
Purpose: Skeletal muscle growth and regeneration rely on muscle stem cells, called satellite cells. Specific transcription factors, particularly PAX7, are key regulators of the function of these cells. Knockout of this factor in mice leads to poor postnatal survival; however, the consequences of a lack of PAX7 in humans have not been established....
Article
Loss of dystrophin expression in Duchenne muscular dystrophy (DMD) causes progressive degeneration of skeletal muscle, which is exacerbated by reduced self-renewing asymmetric divisions of muscle satellite cells. This, in turn, affects the production of myogenic precursors and impairs regeneration and suggests that increasing such divisions may be...
Chapter
The regenerative capacity of skeletal muscle is due to a population of satellite cells known as satellite stem cells. Owing to their ability to generate both stem cells and committed myogenic progenitors, satellite stem cells allow self-renewal of the satellite cell reservoir and provide myogenic progenitor cells to repair the muscle tissue. Increa...
Article
Full-text available
Anti-inflammatory modalities are commonly used for the treatment of various musculoskeletal injuries. Although inflammation was originally believed to interfere with skeletal muscle regeneration, several recent studies have highlighted the beneficial effects of inflammatory cells on muscle healing. This discrepancy is attributable to an evolving un...
Chapter
Full-text available
Muscle stem cells, named satellite cells, are quiescent in resting skeletal muscle. Following injury, satellite cells are activated and become proliferating myoblasts that either self-renew or differentiate. Several markers are used to identify the different myogenic populations, such as Pax7 (quiescent and activated satellite cells), MyoD (prolife...
Article
Full-text available
Age-related changes in the niche have long been postulated to impair the function of somatic stem cells. Here we demonstrate that the aged stem cell niche in skeletal muscle contains substantially reduced levels of fibronectin (FN), leading to detrimental consequences for the function and maintenance of muscle stem cells (MuSCs). Deletion of the ge...
Article
Duchenne muscular dystrophy (DMD) is a genetic disease characterised by skeletal muscle degeneration and progressive muscle wasting, which is caused by loss-of-function mutations in the DMD gene that encodes for the protein dystrophin. Dystrophin has critical roles in myofiber stability and integrity by connecting the actin cytoskeleton to the extr...
Article
Muscle injuries are very frequent and are associated with an inflammatory reaction that varies in intensity. Classically the inflammatory process was considered harmful for muscle regeneration and anti-inflammatory agents are still part of a conventional therapy. Over the last decades, it has been demonstrated under some conditions that the inflamm...
Article
Full-text available
Receptor-activator of nuclear factor kB (RANK), its ligand RANKL and the soluble decoy receptor osteoprotegerin (OPG) are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion (RANK(mko)) has inotropic effects in dener...
Article
Full-text available
Dystrophin is expressed in differentiated myofibers, in which it is required for sarcolemmal integrity, and loss-of-function mutations in the gene that encodes it result in Duchenne muscular dystrophy (DMD), a disease characterized by progressive and severe skeletal muscle degeneration. Here we found that dystrophin is also highly expressed in acti...
Article
Full-text available
Significance Satellite cells form the resident stem cell population in adult skeletal muscle, providing the foundation for postnatal growth and repair of this tissue. Satellite cell self-renewal is maintained by the paired-box transcription factor Pax7, suggesting that this protein is a key determinant in managing cell fate decisions for this niche...
Article
Full-text available
Skeletal muscles are essential for vital functions such as movement, postural support, breathing, and thermogenesis. Muscle tissue is largely composed of long, postmitotic multinucleated fibers. The life-long maintenance of muscle tissue is mediated by satellite cells, lying in close proximity to the muscle fibers. Muscle satellite cells are a hete...
Article
Full-text available
Muscle stem cells, termed satellite cells, are crucial for skeletal muscle growth and regeneration. In healthy adult muscle, satellite cells are quiescent but poised for activation. During muscle regeneration, activated satellite cells transiently re-enter the cell cycle to proliferate and subsequently exit the cell cycle to differentiate or self-r...
Article
Receptor-activator of NF-κB, its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Although there is a strong association between osteoporosis and skeletal muscle atrophy/dysfunction, the functional relevance of a particular biological pathway that synchronously re...
Article
Full-text available
Muscle stem cells facilitate the long-term regenerative capacity of skeletal muscle. This self-renewing population of satellite cells has only recently been defined through genetic and transplantation experiments. Although muscle stem cells remain in a dormant quiescent state in uninjured muscle, they are poised to activate and produce committed pr...
Article
Full-text available
Diminished regenerative capacity of skeletal muscle occurs during adulthood. We identified a reduction in the intrinsic capacity of mouse adult satellite cells to contribute to muscle regeneration and repopulation of the niche. Gene expression analysis identified higher expression of JAK-STAT signaling targets in 3-week-old relative to 18-month-old...
Article
Full-text available
Wnt7a/Fzd7 signaling stimulates skeletal muscle growth and repair by inducing the symmetric expansion of satellite stem cells through the planar cell polarity pathway and by activating the Akt/mTOR growth pathway in muscle fibers. Here we describe a third level of activity where Wnt7a/Fzd7 increases the polarity and directional migration of mouse s...
Article
Full-text available
Satellite cells, the quintessential skeletal muscle stem cells, reside in a specialized local environment whose anatomy changes dynamically during tissue regeneration. The plasticity of this niche is attributable to regulation by the stem cells themselves and to a multitude of functionally diverse cell types. In particular, immune cells, fibrogenic...
Article
Full-text available
Skeletal muscle injury and regeneration are closely associated with an inflammatory reaction that is usually characterized by sequential recruitment of neutrophils and monocytes or macrophages. Selective macrophage depletion models have shown that macrophages are essential for complete regeneration of muscle fibers after freeze injuries, toxin inju...
Article
Full-text available
Duchenne muscular dystrophy (DMD) still needs effective treatments, and myoblast transplantation (MT) is considered as an approach to repair damaged skeletal muscles. DMD is due to the complete loss of dystrophin from muscles. The lack of link between the contracting apparatus and the extracellular matrix leads to frequent damage to the sarcolemma...
Article
Full-text available
Duchenne muscular dystrophy (DMD) is the most frequent muscular dystrophy. Currently, there is no cure for the disease. The transplantation of muscle precursor cells (MPCs) is one of the possible treatments, because it can restore the expression of dystrophin in DMD muscles. In this study, we investigated the effects of myoblasts injected with card...
Article
Full-text available
Hindlimb unloading and reloading are characterized by a major loss of muscle force and are associated with classic leukocyte infiltration during recovery from muscle atrophy. Macrophages act as a cellular cornerstone by playing both pro- and anti-inflammatory roles during muscle recovery from atrophy. In the present study, we investigated the role...
Article
Full-text available
Neutrophils phagocyte necrotic debris and release cytokines, enzymes, and oxidative factors. In the present study, we investigated the contribution of neutrophils to muscle injury, dysfunction, and recovery using an unloading and reloading model. Mice were submitted to 10 days of hindlimb unloading and were transiently depleted in neutrophils with...
Article
Full-text available
Rodent hindlimb suspension is widely used to induce inflammation and muscle impairment. We set out to define the role of mast cells in neutrophil and macrophage recruitment and muscle recovery after unloading-reloading. We hypothesized that mechanical perturbation would stimulate release of proinflammatory substances by mast cells, which would infl...

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