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Publication : Six1 regulates stem cell repair potential and self-renewal during skeletal muscle regeneration.

First Author  Le Grand F Year  2012
Journal  J Cell Biol Volume  198
Issue  5 Pages  815-32
PubMed ID  22945933 Mgi Jnum  J:190460
Mgi Id  MGI:5448889 Doi  10.1083/jcb.201201050
Citation  Le Grand F, et al. (2012) Six1 regulates stem cell repair potential and self-renewal during skeletal muscle regeneration. J Cell Biol 198(5):815-32
abstractText  Satellite cells (SCs) are stem cells that mediate skeletal muscle growth and regeneration. Here, we observe that adult quiescent SCs and their activated descendants expressed the homeodomain transcription factor Six1. Genetic disruption of Six1 specifically in adult SCs impaired myogenic cell differentiation, impaired myofiber repair during regeneration, and perturbed homeostasis of the stem cell niche, as indicated by an increase in SC self-renewal. Six1 regulated the expression of the myogenic regulatory factors MyoD and Myogenin, but not Myf5, which suggests that Six1 acts on divergent genetic networks in the embryo and in the adult. Moreover, we demonstrate that Six1 regulates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway during regeneration via direct control of Dusp6 transcription. Muscles lacking Dusp6 were able to regenerate properly but showed a marked increase in SC number after regeneration. We conclude that Six1 homeoproteins act as a rheostat system to ensure proper regeneration of the tissue and replenishment of the stem cell pool during the events that follow skeletal muscle trauma.
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