Pluripotent stem cells hold great potential for regenerative medicine. Increased replication and division, such is the case during regeneration, concomitantly increases the risk of adverse outcomes through the acquisition of mutations. Seeking for driving mechanisms of such outcomes, we challenged a pluripotent stem cell system during the tightly controlled regeneration process in the planarian Schmidtea mediterranea Exposure to the genotoxic compound methyl methanesulfonate (MMS) revealed that despite a similar DNA-damaging effect along the anteroposterior axis of intact animals, responses differed between anterior and posterior fragments after amputation. Stem cell proliferation and differentiation proceeded successfully in the amputated heads, leading to regeneration of missing tissues. Stem cells in the amputated tails showed decreased proliferation and differentiation capacity. As a result, tails could not regenerate. Interference with the body-axis-associated component β-catenin-1 increased regenerative success in tail fragments by stimulating proliferation at an early time point. Our results suggest that differences in the Wnt signalling gradient along the body axis modulate stem cell responses to MMS.

中文翻译：

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DNA 损伤后的再生反应 - β-连环蛋白介导涡虫 Schmidtea mediterranea 的头部再生。

多能干细胞在再生医学方面具有巨大的潜力。复制和分裂的增加（例如再生过程中的情况）会同时增加通过获得突变而产生不良结果的风险。为了寻找此类结果的驱动机制，我们在地中海真涡虫严格控制的再生过程中对多能干细胞系统提出了挑战。暴露于基因毒性化合物甲磺酸甲酯 (MMS) 表明，尽管沿前后轴有类似的 DNA 损伤作用，但对于完整的动物，截肢后前部和后部碎片的反应不同。截肢头部的干细胞增殖和分化成功进行，导致缺失的组织再生。断尾中的干细胞表现出增殖和分化能力下降。结果，尾巴无法再生。干扰与体轴相关的成分 β-catenin-1 通过在早期时间点刺激增殖来增加尾部片段的再生成功率。我们的结果表明，沿身体轴的 Wnt 信号梯度差异调节干细胞对 MMS 的反应。