Dataset Information

Muscle satellite cells and impaired late stage regeneration in different murine models for muscular dystrophies.

ABSTRACT: Satellite cells (SCs) are the main muscle stem cells responsible for its regenerative capacity. In muscular dystrophies, however, a failure of the regenerative process results in muscle degeneration and weakness. To analyze the effect of different degrees of muscle degeneration in SCs behavior, we studied adult muscle of the dystrophic strains: DMDmdx, Largemyd, DMDmdx/Largemyd, with variable histopathological alterations. Similar results were observed in the dystrophic models, which maintained normal levels of PAX7 expression, retained the Pax7-positive SCs pool, and their proliferation capacity. Moreover, elevated expression of MYOG, an important myogenic factor, was also observed. The ability to form new fibers was verified by the presence of dMyHC positive regenerating fibers. However, those fibers had incomplete maturation characteristics, such as small and homogenous fiber caliber, which could contribute to their dysfunction. We concluded that dystrophic muscles, independently of their degeneration degree, retain their SCs pool with proliferating and regenerative capacities. Nonetheless, the maturation of these new fibers is incomplete and do not prevent muscle degeneration. Taken together, these results suggest that the improvement of late muscle regeneration should better contribute to therapeutic approaches.

SUBMITTER: Ribeiro AF

PROVIDER: S-EPMC6694188 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Muscle satellite cells and impaired late stage regeneration in different murine models for muscular dystrophies.

Ribeiro Antonio F AF Souza Lucas S LS Almeida Camila F CF Ishiba Renata R Fernandes Stephanie A SA Guerrieri Danielle A DA Santos André L F ALF Onofre-Oliveira Paula C G PCG Vainzof Mariz M

Scientific reports 20190814 1

Satellite cells (SCs) are the main muscle stem cells responsible for its regenerative capacity. In muscular dystrophies, however, a failure of the regenerative process results in muscle degeneration and weakness. To analyze the effect of different degrees of muscle degeneration in SCs behavior, we studied adult muscle of the dystrophic strains: DMDmdx, Largemyd, DMDmdx/Largemyd, with variable histopathological alterations. Similar results were observed ...[more]

PMID: 31413358

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Project description:Muscular dystrophies and congenital myopathies arise from specific genetic mutations causing skeletal muscle weakness that reduces quality of life. Muscle health relies on resident muscle stem cells called satellite cells, which enable life-course muscle growth, maintenance, repair and regeneration. Such tuned plasticity gradually diminishes in muscle diseases, suggesting compromised satellite cell function. A central issue however, is whether the pathogenic mutation perturbs satellite cell function directly and/or indirectly via an increasingly hostile microenvironment as disease progresses. Here, we explore the effects on satellite cell function of pathogenic mutations in genes (myopathogenes) that associate with muscle disorders, to evaluate clinical and muscle pathological hallmarks that define dysfunctional satellite cells. We deploy transcriptomic analysis and comparison between muscular dystrophies and myopathies to determine the contribution of satellite cell dysfunction using literature, expression dynamics of myopathogenes and their response to the satellite cell regulator PAX7. Our multimodal approach extends current pathological classifications to define Satellite Cell-opathies: muscle disorders in which satellite cell dysfunction contributes to pathology. Primary Satellite Cell-opathies are conditions where mutations in a myopathogene directly affect satellite cell function, such as in Progressive Congenital Myopathy with Scoliosis (MYOSCO) and Carey-Fineman-Ziter Syndrome (CFZS). Primary satellite cell-opathies are generally characterised as being congenital with general hypotonia, and specific involvement of respiratory, trunk and facial muscles, although serum CK levels are usually within the normal range. Secondary Satellite Cell-opathies have mutations in myopathogenes that affect both satellite cells and muscle fibres. Such classification aids diagnosis and predicting probable disease course, as well as informing on treatment and therapeutic development.

Dataset Information

Muscle satellite cells and impaired late stage regeneration in different murine models for muscular dystrophies.

Publications

Muscle satellite cells and impaired late stage regeneration in different murine models for muscular dystrophies.

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