i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
Vertebrate Development and Regeneration Group, IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal.
Cells. 2021 May 18;10(5):1241. doi: 10.3390/cells10051241.
is a master regulator of the cell cycle, contributing to cell proliferation. Recent data have shown that this transcription factor also modulates gene networks associated with other cellular mechanisms, suggesting non-proliferative functions that remain largely unexplored. In this study, we used CRISPR/Cas9 to disrupt in the zebrafish terminally differentiated fast-twitching muscle cells. genomic disruption increased myofiber death and clearance. Interestingly, this contributed to non-autonomous satellite cell activation and proliferation. Moreover, we observed that Cas9 expression alone was strongly deleterious to muscle cells. Our report shows that modulates a muscle non-autonomous response to myofiber death and highlights underreported toxicity to high expression of Cas9 in vivo.
是细胞周期的主要调节因子，促进细胞增殖。最近的数据表明，这种转录因子还调节与其他细胞机制相关的基因网络，提示存在大量尚未探索的非增殖性功能。在这项研究中，我们使用 CRISPR/Cas9 技术破坏斑马鱼终末分化的快收缩肌细胞中的 。基因组缺失增加了肌纤维的死亡和清除。有趣的是，这导致非自主卫星细胞的激活和增殖。此外，我们观察到 Cas9 表达本身对肌肉细胞具有很强的毒性。我们的报告表明 调节肌肉对肌纤维死亡的非自主性反应，并强调了体内高表达 Cas9 的报道较少的毒性。
