Lkb1 deletion upregulates Pax7 expression through activating Notch signaling pathway in myoblasts

Satellite cells play crucial roles in mediating the growth, maintenance, and repair of postnatal skeletal muscle. Activated satellite cells (myoblasts) can divide symmetrically or asymmetrically to generate progenies that self-renewal, proliferate or differentiate. Pax7 is a defining marker of quiescent and activated satellite cells, but not differentiated myoblast. We demonstrate here that deletion of Lkb1 upregulates Pax7 expression in myoblasts and inhibits asymmetric divisions that generate differentiating progenies. Furthermore, we find that Lkbl activates the Notch signaling pathway, which subsequently increases Pax7 expression and promotes self-renewal and proliferation while inhibiting differentiation. Mechanistic studies reveal that Lkbl regulates Notch activation through AMPK-mTOR pathway in myoblasts. Together, these results establish a key role of Lkbl in regulating myoblast division and cell fates choices. (C) 2016 Elsevier Ltd. All rights reserved.