Biology subjects

Hibbert, J. E.

Publications and source records attributed to Hibbert, J. E..

3 recordsLinked to original sources

bioRxiv2023

The role of satellite cell-derived TRIM28 in mechanical load- and injury-induced myogenesis

Satellite cells are skeletal muscle stem cells that contribute to postnatal muscle growth, and they endow skeletal muscle with the ability to regenerate after a severe injury. Here we discovered that this myogenic potential of satellite cells requires a protein called tripartite motif-containing 28 (TRIM28). Unexpectedly, multiple lines of both in vitro and in vivo evidence revealed that the myogenic function of TRIM28 is not dependent on changes in the phosphorylation of its serine 473 residue. Moreover, the functions of TRIM28 were not mediated through the regulation of satellite cell proliferation or differentiation. Instead, our findings indicate that TRIM28 regulates the ability of satellite cells to progress through the process of fusion. Specifically, we discovered that TRIM28 controls the expression of a fusogenic protein called myomixer and concomitant fusion pore formation. Collectively, the outcomes of this study expose the framework of a novel regulatory pathway that is essential for myogenesis. TeaserTRIM28 regulates the induction of myomixer expression and fusion pore formation during myogenesis.

cell biology↗

bioRxiv2023

A Novel Imaging Method (FIM-ID) Reveals that Myofibrillogenesis Plays a Major Role in the Mechanically Induced Growth of Skeletal Muscle

An increase in mechanical loading, such as that which occurs during resistance exercise, induces radial growth of muscle fibers (i.e., an increase in cross-sectional area). Muscle fibers are largely composed of myofibrils, but whether radial growth is mediated by an increase in the size of the myofibrils (i.e., myofibril hypertrophy) and/or the number of myofibrils (i.e., myofibrillogenesis) is not known. Electron microscopy (EM) can provide images with the level of resolution that is needed to address this question, but the acquisition and subsequent analysis of EM images is a time- and cost-intensive process. To overcome this, we developed a novel method for visualizing myofibrils with a standard fluorescence microscope (FIM-ID). Images from FIM-ID have a high degree of resolution and contrast, and these properties enabled us to develop pipelines for automated measurements of myofibril size and number. After extensively validating the automated measurements, we used both mouse and human models of increased mechanical loading to discover that the radial growth of muscle fibers is largely mediated by myofibrillogenesis. Collectively, the outcomes of this study offer insight into a fundamentally important topic in the field of muscle growth and provide future investigators with a time- and cost-effective means to study it.

cell biology↗

bioRxiv2021

Weight Pulling: A Novel Mouse Model of Human Progressive Resistance Exercise

This study describes a mouse model of progressive resistance exercise that utilizes a full-body/multi-joint exercise (weight pulling) along with a training protocol that mimics a traditional human paradigm (3 training sessions per week, [~]8-12 repetitions per set, 2 minutes of rest between sets, [~]2 maximal-intensity sets per session, last set taken to failure, and a progressive increase in loading that is based on the individuals performance). We demonstrate that weight pulling can induce an increase in the mass of numerous muscles throughout the body. The relative increase in muscle mass is similar to what has been observed in human studies, and it is associated with the same type of long-term adaptations that occur in humans (e.g., fiber hypertrophy, myonuclear accretion, and in some instances a fast-to-slow transition in Type II fiber composition). Moreover, we demonstrate that weight pulling can induce the same type of acute responses that are thought to drive these long-term adaptations (e.g., the activation of signaling through mTORC1 and the induction of protein synthesis at 1 hr post-exercise). Collectively, the results of this study indicate that weight pulling can serve as a highly translatable mouse model of progressive resistance exercise.

physiology↗