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Expression data in muscle cells (myotubes) of motor neuron disorders (ALS, SBMA, SMA-IV) and healthy controls

ABSTRACT: Despite the discovery of many genetic risk factors, the cause of the motor neuron death that drives terminal pathology in Amyotrophic Lateral Sclerosis (ALS) remains unknown. We report that the skeletal muscle of ALS patients secretes exosomal vesicles that are specifically toxic to motor neurons. This could not be attributed to a trivial down-stream consequence of muscle denervation. In a study of muscle biopsies and biopsy-derived denervation-naïve differentiated muscle stem cells (myotubes) from 67 human subjects, including healthy and disease controls, ALS myotubes had a consistent signature of disrupted exosome biogenesis and RNA-processing, and their exosomes induced shortened, less branched, neurites, greater death, and disrupted localization of RNA and RNA-processing proteins in motor neurons. Toxicity was dependent on presence of the FUS protein, which is highly expressed in recipient motor neurons. As part of this work, we carried out gene expression analysis of myotubes (differentiated myoblasts) comparing ALS against two other motor neuron disorders as disease controls (SBMA, Spinal and bulbar muscular atrophy; and Spinal Muscular Atrophy Type 4, SMA-IV) and healthy controls.

ORGANISM(S): Homo sapiens

PROVIDER: GSE122261 | GEO | 2022/04/19

REPOSITORIES: GEO

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