Stress and stem cells: adult Muse cells tolerate extensive genotoxic stimuli better than mesenchymal stromal cells.
Stress and stem cells: adult Muse cells tolerate extensive genotoxic stimuli better than mesenchymal stromal cells.
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DOI：
10.18632/oncotarget.25039
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发表时间：
2018-04-10
期刊：
影响因子：
--
通讯作者：
Galderisi U
中科院分区：
文献类型：
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作者：
Alessio N;Squillaro T;Özcan S;Di Bernardo G;Venditti M;Melone M;Peluso G;Galderisi U
间充质基质细胞(MSCs)不是一个同质的群体，但包括几种细胞类型，如干细胞、前体细胞、成纤维细胞和其他类型的细胞。其中包括多能干细胞，约占骨髓间充质干细胞的1-3%。这些细胞被称为多系分化应激耐受(MUSE)细胞，是耐受胁迫的细胞。由于干细胞的长寿命，它们可能会经历几轮内在和外在的应激，必须有一个强大而有效的DNA损伤检查点和DNA修复机制，在发生遗传毒性事件后，促进细胞的完全恢复，而不是引发衰老和/或凋亡。与MSCs相比，我们评估了MUSE细胞如何应对DNA损伤应激。我们发现MUSE细胞比非MUSE细胞对化学和物理遗传毒性应激具有更好的抗性。事实上，MUSE细胞的衰老和凋亡水平较低。我们的结果证明，小鼠细胞损伤后，DNA损伤修复系统(DDR)被适当地激活。而在非缪斯细胞中，可能发生了一些异常，因为在某些情况下，DDR的激活持续到损伤后48小时，在另一些情况下没有激活。在MUSE细胞中，与其他细胞相比，非同源末端连接(NHEJ)酶活性增加，而单链修复活性(NER，BER)不增加。综上所述，MUSE细胞应对遗传毒性应激的高能力与其快速有效地感知DNA损伤和激活DNA修复系统有关。
Mesenchymal stromal cells (MSCs) are not a homogenous population but comprehend several cell types, such as stem cells, progenitor cells, fibroblasts, and other types of cells. Among these is a population of pluripotent stem cells, which represent around 1–3% of MSCs. These cells, named multilineage-differentiating stress enduring (Muse) cells, are stress-tolerant cells. Stem cells may undergo several rounds of intrinsic and extrinsic stresses due to their long life and must have a robust and effective DNA damage checkpoint and DNA repair mechanism, which, following a genotoxic episode, promote the complete recovery of cells rather than triggering senescence and/or apoptosis. We evaluated how Muse cells can cope with DNA damaging stress in comparison with MSCs. We found that Muse cells were resistant to chemical and physical genotoxic stresses better than non-Muse cells. Indeed, the level of senescence and apoptosis was lower in Muse cells. Our results proved that the DNA damage repair system (DDR) was properly activated following injury in Muse cells. While in non-Muse cells some anomalies may have occurred because, in some cases, the activation of the DDR persisted by 48 hr post damage, in others no activation took place. In Muse cells, the non-homologous end joining (NHEJ) enzymatic activity increases compared to other cells, while single-strand repair activity (NER, BER) does not. In conclusion, the high ability of Muse cells to cope with genotoxic stress is related to their quick and efficient sensing of DNA damage and activation of DNA repair systems.