Immunomyoblasts in muscle regeneration

点击翻译按钮获取中文摘要

Abstract Satellite cells are muscle-resident stem cells responsible for postnatal muscle growth, maintenance and regeneration. In response to muscle injury, quiescent satellite cells are activated, enter the cell cycle and proliferate, then differentiate to repair the injury or self-renew to replenish the satellite cell pool. In order for satellite cells to regenerate injured muscles, the cells have to interact and coordinate with a number of other resident and infiltrating cells during the regeneration. The cell-cell communication is crucial for efficient muscle regeneration but how different types cells interact in the regenerating muscle is poorly understood. We have recently employed single cell RNA sequencing (scRNA-seq) to dissect the various cell populations and they interactions during muscle regeneration. This scRNA-seq analysis identifies a new subset of satellite cells with an immune gene signature that allows them to uniquely interact with the immune cells. We call these cells immunomyoblasts (IMBs). The existence of IMBs in regenerating muscle is also confirmed by another independent scRNA-seq study and the immune gene signature is confirmed in our preliminary studies. The discovery of IMBs not only adds a new dimension of heterogeneity to satellite cells but also opens a new avenue to understand how satellite cells communicate with immune cells to accomplish timely resolution of inflammation and completion of regeneration. Based on this exciting discovery, the overall goal of this proposed study is therefore to explore the origin, dynamics and physiological function of IMBs; and elucidate the regulatory pathways that underlie the function of IMBs. Upon completion of the project, we will fill an important knowledge gap on the biology of the newly discovered IMBs. Such knowledge will provide an immediate clear picture underlying the bilateral crosstalk between satellite cells and immune cells. In the long-run, the knowledge from this work will have important implications in developing novel strategies to modulate the IMB– immune cell crosstalk to improve the regenerative capacity of damaged or degenerated muscles in response to acute injury or under degenerative disease conditions.