Lsd1 Regulates Skeletal Muscle Regeneration And Directs The Fate Of Satellite Cells

[Terma]

2018 Jan 25

Lsd1 regulates skeletal muscle regeneration and directs the fate of satellite cells

Satellite cells are muscle stem cells required for muscle regeneration upon damage. Of note, satellite cells are bipotent and have the capacity to differentiate not only into skeletal myocytes, but also into brown adipocytes. Epigenetic mechanisms regulating fate decision and differentiation of satellite cells during muscle regeneration are not yet fully understood. Here, we show that elevated levels of lysine-specific demethylase 1 (Kdm1a, also known as Lsd1) have a beneficial effect on muscle regeneration and recovery after injury, since Lsd1 directly regulates key myogenic transcription factor genes. Importantly, selective Lsd1 ablation or inhibition in Pax7-positive satellite cells, not only delays muscle regeneration, but changes cell fate towards brown adipocytes. Lsd1 prevents brown adipocyte differentiation of satellite cells by repressing expression of the novel pro-adipogenic transcription factor Glis1. Together, downregulation of Glis1 and upregulation of the muscle-specific transcription program ensure physiological muscle regeneration.

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Taken together our results implicate that physiological levels of Lsd1 are necessary for normal muscle regeneration after injury. Elevated levels of Lsd1 might be beneficial and accelerate the process of muscle regeneration, whereas loss or inhibition of Lsd1 leads to aberrant differentiation and acquisition of a brown fat phenotype. Lsd1 therefore, not only promotes muscle differentiation, but also restricts the fate of satellite cells to the myogenic lineage.

This was so cool had to make an effort to post it somewhere. (otherwise, can't post anymore, cheers adios)

 

[paymanz]

thx,sub'd.