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类器官培养促进小鼠肌母细胞去分化为能够完全再生肌肉的干细胞
作者:小柯机器人 发布时间:2024/9/12 19:33:33

美国哈佛大学等研究人员合作发现,类器官培养促进小鼠肌母细胞去分化为能够完全再生肌肉的干细胞。相关论文于2024年9月11日发表在《自然—生物技术》杂志上。

研究人员提出了一种从骨骼肌组织生成体外衍生卫星细胞(idSC)的方法。当少量小鼠idSC移植到小鼠肌肉中时,它们能够融合到肌纤维中,重新填充卫星细胞的微环境,自我更新,支持多轮肌肉再生,并在受损骨骼肌中提高与新鲜分离的卫星细胞相当的肌肉力量。

研究人员比较了idSC、肌母细胞和卫星细胞的表观基因组和转录组特征,并利用这些特征识别赋予idSC功能的核心信号通路和基因。最后,研究人员成功从人类肌肉活检中体外生成了类似卫星细胞的细胞。经过进一步发展,idSC可能为治疗遗传性肌肉疾病、创伤性肌肉损伤和与年龄相关的肌肉衰弱提供一种可扩展的细胞来源。

据了解,用于骨骼肌疾病的实验性细胞疗法迄今取得的成功有限,主要原因是使用了已定向的成肌祖细胞而非真正的肌肉干细胞(卫星细胞)。

附:英文原文

Title: Organoid culture promotes dedifferentiation of mouse myoblasts into stem cells capable of complete muscle regeneration

Author: Price, Feodor D., Matyas, Mark N., Gehrke, Andrew R., Chen, William, Wolin, Erica A., Holton, Kristina M., Gibbs, Rebecca M., Lee, Alice, Singu, Pooja S., Sakakeeny, Jeffrey S., Poteracki, James M., Goune, Kelsey, Pfeiffer, Isabella T., Boswell, Sarah A., Sorger, Peter K., Srivastava, Mansi, Pfaff, Kathleen Lindahl, Gussoni, Emanuela, Buchanan, Sean M., Rubin, Lee L.

Issue&Volume: 2024-09-11

Abstract: Experimental cell therapies for skeletal muscle conditions have shown little success, primarily because they use committed myogenic progenitors rather than true muscle stem cells, known as satellite cells. Here we present a method to generate in vitro-derived satellite cells (idSCs) from skeletal muscle tissue. When transplanted in small numbers into mouse muscle, mouse idSCs fuse into myofibers, repopulate the satellite cell niche, self-renew, support multiple rounds of muscle regeneration and improve force production on par with freshly isolated satellite cells in damaged skeletal muscle. We compared the epigenomic and transcriptional signatures between idSCs, myoblasts and satellite cells and used these signatures to identify core signaling pathways and genes that confer idSC functionality. Finally, from human muscle biopsies, we successfully generated satellite cell-like cells in vitro. After further development, idSCs may provide a scalable source of cells for the treatment of genetic muscle disorders, trauma-induced muscle damage and age-related muscle weakness.

DOI: 10.1038/s41587-024-02344-7

Source: https://www.nature.com/articles/s41587-024-02344-7

期刊信息

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:68.164
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex