Coordination of Satellite Cell Activation and Self-Renewal by Par-Complex-Dependent Asymmetric Activation of p38α/β MAPK

Abstract

SUMMARY In response to muscle injury, satellite cells activate the p38α/β MAPK pathway to exit quiescence, then proliferate, repair skeletal muscle, and self-renew, replenishing the quiescent satellite cell pool. Although satellite cells are capable of asymmetric division, the mechanisms regulating satellite cell self-renewal are not understood. We found that satellite cells, once activated, enter the cell cycle and a subset undergoes asymmetric division, renewing the satellite cell pool. Asymmetric localization of the Par complex activates p38α/β MAPK in only one daughter cell, inducing MyoD, which permits cell cycle entry and generates a proliferating myoblast. The absence of p38α/β MAPK signaling in the other daughter cell prevents MyoD induction, renewing the quiescent satellite cell. Thus, satellite cells employ a mechanism to generate distinct daughter cells, coupling the Par complex and p38α/β MAPK signaling to link the response to muscle injury with satellite cell self-renewal.

TRAF6 regulates satellite stem cell self-renewal and function during regenerative myogenesis

“…We next sought to determine whether TRAF6 is required for the expression of PAX7 in satellite cells. Our Western blot analysis confirmed that treatment in promoting progression through the myogenic lineage (32,33). Remarkably, we found that phosphorylated and total protein levels of c-JUN, a direct phosphorylation target of ERK1/2 and JNK, were also significantly diminished as a result of deletion of Traf6 ( Figure 6, E and F).…”

Synergistic effects of TGFβ2, WNT9a, and FGFR4 signals attenuate satellite cell differentiation during skeletal muscle development

“…The WNT and TGFβ signaling pathways could induce the fibrogenesis of satellite cells in dystrophic mice (Biressi, Miyabara, Gopinath, Carlig & Rando, 2014). The TNF, AKT, and MAPK signaling pathways participate in the proliferation and differentiation of satellite cells (Motohashi et al., 2013; Troy et al., 2012). However, the synergistic effects of different signaling pathways remain largely unknown.…”

Cancer Stem Cell Division: When the Rules of Asymmetry Are Broken

“…Current understanding has relied on a limited number of sources, with Drosophila being the prime model used to study division properties of neuroblasts, germline stem cells, and intestinal stem cells [1]. In mammalian systems, most advances have been made through the study of mouse radial glial progenitors [4], neocortical progenitors [5], and muscle satellite cells [6]. The more recent recognition of a stem cell population in cancer has led to investigations of asymmetric cell division in this disease, using mammalian systems and Drosophila as models.…”