Immunomyoblasts in muscle regeneration

免疫成肌细胞在肌肉再生中的作用

• 批准号: 10402924
• 负责人: Shihuan Kuang
• 金额: $ 44.25万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-10 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10402924
• 关键词: Acute; Aging; Anti-Inflammatory Agents; Antigen-Presenting Cells; Bilateral; Biology; Cell Communication; Cell Cycle; Cell Proliferation; Cells; Coculture Techniques; Coin; Data; Degenerative Disorder; Development; Dimensions; Disease; Fluorescence-Activated Cell Sorting; Future; Gene Expression; Genes; Goals; Growth; Heterogeneity; Immune; Immune response; Immune system; Immunologic Markers; Inflammation; Inflammatory; Inflammatory Response; Injury; Knowledge; Light; Maintenance; Maps; Mediating; Molecular; Muscle; Muscle Cells; Muscle satellite cell; Myoblasts; Natural regeneration; Pathologic; Physiological; Population; Population Heterogeneity; Proliferating; Regenerative capacity; Regulation; Regulatory Pathway; Reporting; Resolution; Signal Transduction; Skeletal Muscle; Surveys; Testing; Time; Work; age-related muscle loss; base; cell type; cytokine; gene function; genetic signature; improved; in vivo; injured; injury and repair; muscle regeneration; myogenesis; novel; novel strategies; postnatal; reconstruction; recruit; regeneration function; regenerative; repaired; response; response to injury; satellite cell; self-renewal; single-cell RNA sequencing; stem cell function; stem cells; tissue stem cells

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.

抽象的 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 再生。为了应对肌肉损伤，静止的卫星细胞被激活，进入细胞周期并 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 卫星细胞要再生受伤的肌肉，这些细胞必须与许多其他细胞相互作用和协调 再生过程中的常驻细胞和浸润细胞。细胞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却知之甚少。 我们最近采用单细胞 RNA 测序 (scRNA-seq) 来剖析各种细胞群 它们在肌肉再生过程中相互作用。该 scRNA-seq 分析确定了一个新的子集 卫星细胞具有免疫基因特征，使它们能够与免疫细胞进行独特的相互作用。我们 将这些细胞称为免疫成肌细胞（IMB）。再生肌肉中 IMB 的存在也得到证实 通过另一项独立的 scRNA-seq 研究，免疫基因特征在我们的初步研究中得到证实 研究。 IMB 的发现不仅为卫星细胞增加了异质性的新维度，而且 开辟了一条新途径来了解卫星细胞如何与免疫细胞通信以及时完成任务 炎症消退和再生完成。基于这一令人兴奋的发现，总体目标 因此，这项研究的目的是探索 IMB 的起源、动力学和生理功能；和 阐明 IMB 功能背后的调控途径。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。这些知识将提供 卫星细胞和免疫细胞之间双边串扰的直接清晰图像。在 从长远来看，这项工作的知识将对制定新的战略产生重要影响 调节IMB-免疫细胞串扰以提高受损或退化的再生能力 肌肉对急性损伤或退行性疾病条件的反应。