Targeting PKC? Promotes Satellite Cell Self-Renewal.

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

SUBMITTER: Benedetti A 

PROVIDER: S-EPMC7177808 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature