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

First Author  Tosic M Year  2018
Journal  Nat Commun Volume  9
Issue  1 Pages  366
PubMed ID  29371665 Mgi Jnum  J:260096
Mgi Id  MGI:6114929 Doi  10.1038/s41467-017-02740-5
Citation  Tosic M, et al. (2018) Lsd1 regulates skeletal muscle regeneration and directs the fate of satellite cells. Nat Commun 9(1):366
abstractText  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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