MyoGravity 项目,研究微重力对人体肌肉前体细胞和组织的实际影响。

IF 4.4 1区 物理与天体物理 Q1 MULTIDISCIPLINARY SCIENCES npj Microgravity Pub Date : 2024-10-03 DOI:10.1038/s41526-024-00432-1
Ester Sara Di Filippo, Sara Chiappalupi, Stefano Falone, Vincenza Dolo, Fernanda Amicarelli, Silvia Marchianò, Adriana Carino, Gabriele Mascetti, Giovanni Valentini, Sara Piccirillo, Michele Balsamo, Marco Vukich, Stefano Fiorucci, Guglielmo Sorci, Stefania Fulle
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引用次数: 0

摘要

太空飞行期间经历的微重力(µG)促进了宇航员多个器官和组织的适应,其中骨骼肌受到的影响最大。为了应对重力负荷的降低,肌肉(尤其是下肢肌肉和反重力肌肉)的质量会逐渐下降,新陈代谢、肌纤维大小和成分也会发生变化。骨骼肌前体细胞(MPCs)又称卫星细胞,负责成年后肌肉质量的生长和维持,以及肌肉受损后的再生,可能在 µG 诱导的肌肉萎缩中扮演重要角色。尽管µG 与宇航员的健康息息相关,但有关实际 µG 对人体肌肉影响的数据却寥寥无几。基于 MyoGravity 项目,本研究旨在分析:(i) 真实 µG 在人类 MPCs(huMPCs)中诱导的细胞和转录变化;(ii) 人类骨骼肌在长期暴露于 µG 后对正常重力负荷的反应。我们评估了µG 在国际空间站(ISS)上对从一名飞行前宇航员和一名年龄与性别匹配的志愿者的腹外肌活检组织中分离出来的分化 huMPCs 所诱导的转录组变化,并与在地面标准重力(1×g)条件下培养的相同细胞进行了比较。我们发现,在真实 µG 条件下分化的 huMPCs 表现出以下特征(i) 与细胞粘附、质膜成分和离子转运有关的基因上调;(ii) 与肌肉收缩机制和肌节组织有关的基因强烈下调;(iii) 肌肉特异性 microRNAs(myomiRs)下调。此外,我们还获得了一个独特的机会,在国际空间站上进行长时间太空飞行之前和之后 30 小时,对同一宇航员的 huMPCs 和骨骼肌组织进行了分析。长期暴露在真实微戈(real µG)环境中对宇航员卫星细胞的生物学和功能产生了强烈影响,卫星细胞对活化刺激的反应性和增殖率急剧下降,形态发生变化,几乎无法融合成肌管。对飞行后与飞行前的肌肉组织进行的RNA-Seq分析表明,参与肌肉结构和重塑的基因在长时间太空任务后着陆后迅速被激活。相反,参与髓鞘化过程或突触和神经肌肉接头组织的基因则出现了下调。虽然我们只对一名宇航员进行了研究,但这些结果表明,骨骼肌的机械成分能迅速重新适应正常的重力负荷,但从长期太空飞行中着陆后,无法迅速恢复生理性的肌肉髓鞘化/神经支配模式。再加上在宇航员的卫星细胞中观察到的长期暴露于真实微戈后的持续功能缺陷,这些结果使我们推测,飞行后宇航员的肌肉在受损后很可能会出现低效再生的情况。
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The MyoGravity project to study real microgravity effects on human muscle precursor cells and tissue.

Microgravity (µG) experienced during space flights promotes adaptation in several astronauts' organs and tissues, with skeletal muscles being the most affected. In response to reduced gravitational loading, muscles (especially, lower limb and antigravity muscles) undergo progressive mass loss and alteration in metabolism, myofiber size, and composition. Skeletal muscle precursor cells (MPCs), also known as satellite cells, are responsible for the growth and maintenance of muscle mass in adult life as well as for muscle regeneration following damage and may have a major role in µG-induced muscle wasting. Despite the great relevance for astronaut health, very few data are available about the effects of real µG on human muscles. Based on the MyoGravity project, this study aimed to analyze: (i) the cellular and transcriptional alterations induced by real µG in human MPCs (huMPCs) and (ii) the response of human skeletal muscle to normal gravitational loading after prolonged exposure to µG. We evaluated the transcriptomic changes induced by µG on board the International Space Station (ISS) in differentiating huMPCs isolated from Vastus lateralis muscle biopsies of a pre-flight astronaut and an age- and sex-matched volunteer, in comparison with the same cells cultured on the ground in standard gravity (1×g) conditions. We found that huMPCs differentiated under real µG conditions showed: (i) upregulation of genes related to cell adhesion, plasma membrane components, and ion transport; (ii) strong downregulation of genes related to the muscle contraction machinery and sarcomere organization; and (iii) downregulation of muscle-specific microRNAs (myomiRs). Moreover, we had the unique opportunity to analyze huMPCs and skeletal muscle tissue of the same astronaut before and 30 h after a long-duration space flight on board the ISS. Prolonged exposure to real µG strongly affected the biology and functionality of the astronaut's satellite cells, which showed a dramatic reduction of responsiveness to activating stimuli and proliferation rate, morphological changes, and almost inability to fuse into myotubes. RNA-Seq analysis of post- vs. pre-flight muscle tissue showed that genes involved in muscle structure and remodeling are promptly activated after landing following a long-duration space mission. Conversely, genes involved in the myelination process or synapse and neuromuscular junction organization appeared downregulated. Although we have investigated only one astronaut, these results point to a prompt readaptation of the skeletal muscle mechanical components to the normal gravitational loading, but the inability to rapidly recover the physiological muscle myelination/innervation pattern after landing from a long-duration space flight. Together with the persistent functional deficit observed in the astronaut's satellite cells after prolonged exposure to real µG, these results lead us to hypothesize that a condition of inefficient regeneration is likely to occur in the muscles of post-flight astronauts following damage.

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来源期刊
npj Microgravity
npj Microgravity Physics and Astronomy-Physics and Astronomy (miscellaneous)
CiteScore
7.30
自引率
7.80%
发文量
50
审稿时长
9 weeks
期刊介绍: A new open access, online-only, multidisciplinary research journal, npj Microgravity is dedicated to publishing the most important scientific advances in the life sciences, physical sciences, and engineering fields that are facilitated by spaceflight and analogue platforms.
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