Targeting PKCθ Promotes Satellite Cell Self-Renewal.

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 in SC self-renewal and differentiation. We show that duanyu1531θ is expressed in SCs, and its active form is localized to the chromosomes, centrosomes, and midbody during mitosis. Lack of duanyu1531θ promotes SC symmetric self-renewal division by regulating Pard3 polarity protein localization, without affecting the overall proliferation rate. Genetic ablation of duanyu1531θ 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 duanyu1531θ resulted in a significant expansion of the quiescent SC pool. Finally, we show that lack of duanyu1531θ does not alter the inflammatory milieu after acute injury in muscle, suggesting that the enhanced self-renewal ability of SCs in mice is not due to an alteration in the inflammatory milieu. Together, these results suggest that duanyu1531θ 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.

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