Regenerating human skeletal muscle forms an emerging niche in vivo to support PAX7 cells.

Skeletal muscle stem and progenitor cells including those derived from human pluripotent stem cells (hPSCs) offer an avenue towards personalized therapies and readily fuse to form human-mouse myofibres in vivo. However, skeletal muscle progenitor cells (SMPCs) inefficiently colonize chimeric stem cell niches and instead associate with human myofibres resembling foetal niches. We hypothesized competition with mouse satellite cells (SCs) prevented SMPC engraftment into the SC niche and thus generated an SC ablation mouse compatible with human engraftment.

Duchenne muscular dystrophy disease severity impacts skeletal muscle progenitor cells systemic delivery.

Duchenne muscular dystrophy (DMD) is caused by an out-of-frame mutation in the DMD gene that results in the absence of a functional dystrophin protein, leading to a devastating progressive lethal muscle-wasting disease. Muscle stem cell-based therapy is a promising avenue for improving muscle regeneration. However, despite the efforts to deliver the optimal cell population to multiple muscles most efforts have failed.

Elevated FMR1-mRNA and lowered FMRP - A double-hit mechanism for psychiatric features in men with FMR1 premutations.

Fragile X syndrome (FXS) is caused by a full mutation of the FMR1 gene (>200 CGG repeats and subsequent methylation), such that there is little or no FMR1 protein (FMRP) produced, leading to intellectual disability (ID). Individuals with the premutation allele (55-200 CGG repeats, generally unmethylated) have elevated FMR1 mRNA levels, a consequence of enhanced transcription, resulting in neuronal toxicity and a spectrum of premutation-associated disorders, including the neurodegenerative disorder fragile X-associated tremor/ataxia syndrome (FXTAS). Here we described 14 patients who had both lowered FMRP and elevated FMR1 mRNA levels, representing dual mechanisms of clinical involvement, which may combine features of both FXS and FXTAS.