Publications by authors named "Silvia Di Francescantonio"

Dystrophy-associated fer-1-like protein (dysferlin) conducts plasma membrane repair. Mutations in the DYSF gene cause a panoply of genetic muscular dystrophies. We targeted a frequent loss-of-function, DYSF exon 44, founder frameshift mutation with mRNA-mediated delivery of SpCas9 in combination with a mutation-specific sgRNA to primary muscle stem cells from two homozygous patients.

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Muscular dystrophies are approximately 50 devastating, untreatable monogenic diseases leading to progressive muscle degeneration and atrophy. Gene correction of transplantable cells using CRISPR/Cas9-based tools is a realistic scenario for autologous cell replacement therapies to restore organ function in many genetic disorders. However, muscle stem cells have so far lagged behind due to the absence of methods to isolate and propagate them and their susceptibility to extensive manipulations.

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Article Synopsis
  • Histone deacetylase 4 (HDAC4) is important for muscle function and is elevated in both dystrophic mice and patients with Duchenne muscular dystrophy (DMD), indicating a potential role in the disease process.
  • Researchers created mice without HDAC4 in muscle tissue, which showed worsening symptoms of DMD, including increased muscle fragility and degeneration, as well as compromised satellite cell survival and muscle regeneration.
  • The study suggests that HDAC4 supports membrane repair in muscle cells and that enhancing this mechanism might help improve muscle function and prevent cell death in DMD.
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Background: Aging is associated with a progressive reduction in cellular function leading to poor health and loss of physical performance. Mitochondrial dysfunction is one of the hallmarks of aging; hence, interventions targeting mitochondrial dysfunction have the potential to provide preventive and therapeutic benefits to elderly individuals. Meta-analyses of age-related gene expression profiles showed that the expression of Ahnak1, a protein regulating several signal-transduction pathways including metabolic homeostasis, is increased with age, which is associated with low VO and poor muscle fitness.

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A complex interplay of intrinsic factors and extrinsic signalling pathways controls both cell lineage commitment and maintenance of cell identity. Loss of defined cellular states is the cause of many different cancers, including pancreatic cancer. Recent findings suggest a clinical role for the conserved SLIT/ROBO signalling pathway in pancreatic cancer.

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