Wouters Annelies, Ploem Jan-Pieter, Langie Sabine A S, Artois Tom, Aboobaker Aziz, Smeets Karen
Zoology, Biodiversity and Toxicology, Centre for Environmental Sciences, Hasselt University, 3590 Diepenbeek, Belgium.
Vito Health, 2400 Mol, Belgium.
J Cell Sci. 2020 Apr 24;133(8):jcs237545. doi: 10.1242/jcs.237545.
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 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 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.
多能干细胞在再生医学中具有巨大潜力。在再生过程中，复制和分裂的增加，会通过获取突变相应增加不良后果的风险。为探寻此类后果的驱动机制，我们在涡虫严格受控的再生过程中对一个多能干细胞系统进行了挑战。暴露于基因毒性化合物甲磺酸甲酯（MMS）显示，尽管在完整动物的前后轴上存在类似的DNA损伤效应，但截肢后前后片段的反应有所不同。截肢头部的干细胞增殖和分化成功进行，导致缺失组织的再生。截肢尾部的干细胞显示出增殖和分化能力下降。结果，尾巴无法再生。干扰与身体轴相关的成分，通过在早期刺激增殖，提高了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。
