Immunomyoblasts in muscle regeneration

免疫成肌细胞在肌肉再生中的作用

• 批准号: 10154290
• 负责人: Shihuan Kuang
• 金额: $ 44.69万
• 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/10154290
• 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.

摘要 卫星细胞是肌肉干细胞，负责出生后肌肉的生长、维持和 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 卫星细胞要再生受损的肌肉，这些细胞必须与许多其他细胞相互作用和协调 在再生过程中驻留和渗透的细胞。细胞间的交流是高效的关键。 肌肉再生，但不同类型的细胞如何在再生肌肉中相互作用还知之甚少。 我们最近使用了单细胞rna测序(scrna-seq)来分析不同的细胞群体。 它们在肌肉再生过程中相互作用。这种scRNA-seq分析确定了新的 卫星细胞具有免疫基因签名，使它们能够与免疫细胞进行独特的相互作用。我们 我们称这些细胞为免疫成肌细胞(IMB)。在再生肌肉中也证实了IMBS的存在。 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确认 学习。IMB的发现不仅为卫星细胞增加了一个新的异质性维度，而且还 开辟了一条新的途径来了解卫星细胞如何与免疫细胞通信以及时完成 炎症消退，再生完成。基于这一令人兴奋的发现，总的目标是 因此，这项拟议研究的目的是探索IMB的起源、动力学和生理功能；以及 阐明作为IMB功能基础的调控途径。项目完成后，我们将 填补新发现的IMB生物学方面的重要知识空白。这些知识将提供一种 卫星细胞和免疫细胞之间的双边串扰背后立即清晰的图像。在 从长远来看，这项工作的知识将对制定新的战略具有重要意义 调节IMB免疫细胞串扰以提高受损或退变的再生能力 肌肉在急性损伤或退行性疾病条件下的反应。