240th ENMC workshop: The involvement of skeletal muscle stem cells in the pathology of muscular dystrophies 25–27 January 2019, Hoofddorp, The Netherlands

Morgan, Jennifer E.; Butler‐Browne, Gillian; Muntoni, Francesco; Patel, Ketan

doi:10.1016/j.nmd.2019.07.003

Cited by 2 publications

(1 citation statement)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To clarify the role of ADAMTSL1 in muscle homeostasis, we decided to study it in the context of muscular dystrophy. Indeed, repeated lesions of muscle fibers in patients suffering from Duchenne dystrophy trigger permanent regeneration cycles, finally leading to muscle fibrosis 19 . By integrating public transcriptomic data from the analysis of muscles’ biopsies of Duchenne patients at different stages of the disease, we observed that ADAMTSL1 expression increases sequentially at the three stages of the disease, i.e .…”

Section: Resultsmentioning

confidence: 99%

Alterations of the TGFb-sequestration complex member ADAMTSL1 levels are associated with muscular defects and rhabdomyosarcoma aggressiveness

Juban

Bertrand-Chapel

Meyer

et al. 2023

Preprint

View full text Add to dashboard Cite

Rhabdomyosarcoma (RMS) is the most frequent form of paediatric soft-tissue sarcoma and remains a medical challenge, holding in failure current therapeutic strategies. RMS shares histological features with cells of the muscle lineage and this cancer is thought to arise from malignant transformation of myogenic precursors. It has been proposed that RMS and myogenesis could represent the Jekyll and Hyde of skeletal muscle. The underlying idea is that some early steps of myogenic differentiation are blocked in RMS, and that understanding how the normal process has gone awry could help to decipher the biological underpinnings of tumorigenesis and tumor escape. It is widely agreed that extracellular matrix (ECM) interferes in skeletal muscle regeneration and that defects in ECM components are clinically significant. The challenge is now to decipher actors and mechanisms responsible for the transmission of signals to muscle cells and the subsequent alterations that could be associated with RMS. Using an original transgenic mice model, we show here that ADAMTSL1 is involved in skeletal muscle regeneration. As previously reported for other members of its family, ADAMTSL1 is part of the TGF-b-ECM-sequestering complex and likely positively regulates TGF-b-pathway activity. Last, we observed that ADAMTSL1 expression behaves as a strong prognostic factor in the aggressive fusion-positive RMS and correlates with a neural-like phenotype of tumor cells, resulting from gain of SMAD2/3/4 targets.

show abstract

Section: Resultsmentioning

confidence: 99%

Alterations of the TGFb-sequestration complex member ADAMTSL1 levels are associated with muscular defects and rhabdomyosarcoma aggressiveness

Juban

Bertrand-Chapel

Meyer

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Involvement of muscle satellite cell dysfunction in neuromuscular disorders: Expanding the portfolio of satellite cell-opathies

Ganassi

Zammit

2022

Eur J Transl Myol

View full text Add to dashboard Cite

Neuromuscular disorders are a heterogeneous group of acquired or hereditary conditions that affect striated muscle function. The resulting decrease in muscle strength and motility irreversibly impacts quality of life. In addition to directly affecting skeletal muscle, pathogenesis can also arise from dysfunctional crosstalk between nerves and muscles, and may include cardiac impairment. Muscular weakness is often progressive and paralleled by continuous decline in the ability of skeletal muscle to functionally adapt and regenerate. Normally, the skeletal muscle resident stem cells, named satellite cells, ensure tissue homeostasis by providing myoblasts for growth, maintenance, repair and regeneration. We recently defined 'Satellite Cell-opathies’ as those inherited neuromuscular conditions presenting satellite cell dysfunction in muscular dystrophies and myopathies (doi:10.1016/j.yexcr.2021.112906). Here, we expand the portfolio of Satellite Cell-opathies by evaluating the potential impairment of satellite cell function across all 16 categories of neuromuscular disorders, including those with mainly neurogenic and cardiac involvement. We explore the expression dynamics of myopathogenes, genes whose mutation leads to skeletal muscle pathogenesis, using transcriptomic analysis. This revealed that 45% of myopathogenes are differentially expressed during early satellite cell activation (0 - 5 hours). Of these 271 myopathogenes, 83 respond to Pax7, a master regulator of satellite cells. Our analysis suggests possible perturbation of satellite cell function in many neuromuscular disorders across all categories, including those where skeletal muscle pathology is not predominant. This characterisation further aids understanding of pathomechanisms and informs on development of prognostic and diagnostic tools, and ultimately, new therapeutics.

show abstract

240th ENMC workshop: The involvement of skeletal muscle stem cells in the pathology of muscular dystrophies 25–27 January 2019, Hoofddorp, The Netherlands

Cited by 2 publications

References 43 publications

Alterations of the TGFb-sequestration complex member ADAMTSL1 levels are associated with muscular defects and rhabdomyosarcoma aggressiveness

Alterations of the TGFb-sequestration complex member ADAMTSL1 levels are associated with muscular defects and rhabdomyosarcoma aggressiveness

Involvement of muscle satellite cell dysfunction in neuromuscular disorders: Expanding the portfolio of satellite cell-opathies

Contact Info

Product

Resources

About