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人类骨肌的再生形成了一个新兴的生态,以支持PAX7细胞

Michael R Hicks^1,2,3, Kholoud K Saleh^4,5, Ben Clock⁶

¹Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA. mrhicks1@uci.edu.

Nature cell biology

|November 3, 2023

概括

人类多能干细胞 (hPSCs) 可以产生骨肌前代细胞 (SMPCs) 用于治疗. 切除小鼠卫星细胞 (SC) 允许SMPC植入,揭示ACTC1+肌纤维对SMPC支持至关重要.

科学领域:

再生医学是一种再生医学.
干细胞生物学干细胞生物学
骨肌肉生物学骨肌肉生物学

背景情况:

来自人类多能干细胞 (hPSC) 的骨肌肉干细胞和原始细胞 (SMPC) 显示出治疗潜力.
SMPCs不有效地植入小鼠中,与胎儿样肌纤维相结合,而不是卫星细胞.

研究的目的:

调查小鼠卫星细胞 (SC) 在阻碍SMPC植入方面的作用.
确定特定的肌纤维亚型,这些亚型对于支持SMPC殖民和利基形成至关重要.

主要方法:

创建了一个SC-ablated小鼠模型,用于改进人类SMPC移植.
利用单核RNA测序和空间RNA测序来分析细胞相互作用和基因表达.
开发了可酶诱导的ACTC1贫乏的hPSC,以评估ACTC1+肌纤维的必要性.

主要成果:

在再生过程中,SC剥离导致了短暂的Actc1-表达肌纤维亚型的缺失.
经过SC消去的小鼠显示了支持PAX7+SMPCs的人类肌纤维ACTC1+的增加,使其能够在受伤后重新进入虚构.
由于ACTC1+肌纤维的枯竭,这些肌纤维减少了90%,PAX7+细胞数量减少了100倍.

结论:

表达ACTC1的短暂再生的人类肌纤维对于在体内支持PAX7+SMPCs的位的形成至关重要.
克服与内源性SCs的竞争对于成功的SMPC植入和治疗应用至关重要.
了解肌纤维-利基互动为优化肌肉再生的干细胞治疗提供了洞察力.

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