Immunomyoblasts in muscle regeneration

摘要 卫星细胞是肌肉驻留干细胞，负责出生后肌肉的生长，维持和生长。 再生作为对肌肉损伤的反应，静止的卫星细胞被激活，进入细胞周期， 增殖，然后分化以修复损伤或自我更新以补充卫星细胞库。为了使 为了使受损的肌肉再生，这些细胞必须与许多其他细胞相互作用和协调， 再生过程中的常驻和浸润细胞。细胞与细胞之间的通讯对于高效的 肌肉再生，但不同类型的细胞如何在再生肌肉中相互作用的了解甚少。 我们最近采用单细胞RNA测序（scRNA-seq）来解剖各种细胞群， 它们在肌肉再生过程中相互作用。这种scRNA-seq分析鉴定了一个新的亚组， 具有免疫基因特征的卫星细胞，使它们能够与免疫细胞独特地相互作用。我们 称这些细胞为免疫成肌细胞（IMBs）。同时也证实了再生肌肉中存在内隐微球 通过另一项独立的scRNA-seq研究，免疫基因签名在我们的初步研究中得到证实。 问题研究IMB的发现不仅为卫星细胞的异质性增加了新的维度， 开辟了一条新的途径，以了解卫星细胞如何与免疫细胞沟通，以及时完成 炎症消退和再生完成。基于这一令人兴奋的发现， 因此，这项拟议研究的目的是探讨IMB的起源、动力学和生理功能;以及 阐明IMB功能的调控途径。项目完成后，我们将 填补了新发现的IMB生物学的重要知识空白。这样的知识将提供一个 立即清晰的图片之间的卫星细胞和免疫细胞的双边串扰。在 从长远来看，这项工作的知识将对开发新的战略具有重要意义， 调节IMB-免疫细胞串扰，以改善受损或退化细胞的再生能力， 肌肉对急性损伤或退行性疾病的反应。

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.