Abstract
Skeletal muscle regeneration following injury depends on the ability of satellite cells (SCs) to proliferate, self-renew, and eventually differentiate. The factors that regulate the process of self-renewal are poorly understood. In this study we examined the role of PKCθ in SC self-renewal and differentiation. We show that PKCθ is expressed in SCs, and its active form is localized to the chromosomes, centrosomes, and midbody during mitosis. Lack of PKCθ promotes SC symmetric self-renewal division by regulating Pard3 polarity protein localization, without affecting the overall proliferation rate. Genetic ablation of PKCθ or its pharmacological inhibition in vivo did not affect SC number in healthy muscle. By contrast, after induction of muscle injury, lack or inhibition of PKCθ resulted in a significant expansion of the quiescent SC pool. Finally, we show that lack of PKCθ does not alter the inflammatory milieu after acute injury in muscle, suggesting that the enhanced self-renewal ability of SCs in PKCθ-/- mice is not due to an alteration in the inflammatory milieu. Together, these results suggest that PKCθ plays an important role in SC self-renewal by stimulating their expansion through symmetric division, and it may represent a promising target to manipulate satellite cell self-renewal in pathological conditions.
Highlights
Satellite cells (SCs) are the adult stem cells of skeletal muscle
Satellite cells can exist in a quiescent state in physiological conditions, or as activated/committed progenitors during muscle regeneration [14]
A portion of the isolated cells were cultured in growth medium (GM) for 72h to analyze PKCθ expression in proliferating cells
Summary
Satellite cells (SCs) are the adult stem cells of skeletal muscle. They were first identified by Mauro in 1961who named them satellite cells because of their position between the sarcolemma and the basal lamina of the fiber [1]. We found that lack of PKCθ promotes muscle repair in dystrophic mice, even at advanced stages of the disease, supporting SCs survival and maintenance [13]. Whether this effect was due to reduced inflammation or to a direct role of PKCθ on SCs activity, or both, was still unclear. We show that PKCθ plays a direct role in SCs activity by stimulating their symmetric division and promoting their self-renewal. Our findings suggest that, targeting PKCθ might be a potential novel approach to manipulate SC self-renewal in pathological conditions and improve regeneration
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