CPEB1 in the Activation of Muscle Stem Cells
Muscle stem cells, or satellite cells, are one of the better studied stem cell populations in the body, particularly in the context of aging and loss of stem cell function. The balance of evidence to date indicates that these stem cells remain largely intact and capable in an old individual, but quiescent. Thus there may be comparatively simple ways to active these cells in order to improve maintenance of aged muscle tissue, given a better idea of the regulation of quiescence versus activity. Thus the existence of research programs akin to the one noted here, in which researchers are in search of ways to provoke aged muscle stem cells into greater activity.
Skeletal muscle stem cells, or satellite cells (SCs), are indispensable for repairing damaged muscle and are key targets for treating muscle diseases. In healthy uninjured muscle, these reserve stem cells lie in quiescence, a dormant state, to maintain the resident stem cell pool for future muscle repair. When muscle damage occurs, these quiescent muscle stem cells will quickly "wake up", generating enough muscle progenitor cells to build new muscle. Despite being a critical step in muscle regeneration, the muscle stem cell quiescence-to-activation transition remains an elusive process.
Recently, using a whole mouse perfusion technique to obtain the true quiescent SCs for low-input mass spectrometry analysis, a team of scientists revealed that a regulating protein called CPEB1 is instrumental in reprogramming the translational landscape in SCs, hence driving the cells into activation and proliferation. "Our analysis shows that levels of CPEB1 protein are low in quiescent SCs, but upregulated in activated SCs, with loss of CPEB1 delaying SC activation."
In their subsequent RNA immunoprecipitation sequencing analysis and CPEB1-knockdown proteomic analysis, the researchers found that CPEB1 phosphorylation regulates the expression of the crucial myogenic factor MyoD - a protein involving in skeletal muscle development - by targeting some of the sequences found within the three prime untranslated region (3'UTR) of the target RNA transcript to drive SC activation. "It means that the manipulation of CPEB1 levels or phosphorylation can increase SC proliferation to generate enough myogenic progenitor cells for muscle repair, which could be a potential therapeutic target for muscle repair in the elderly."