DNA damage and tissue repair: What we can learn from planaria.
DNA damage and tissue repair: What we can learn from planaria.
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DOI：
10.1016/j.semcdb.2018.04.013
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发表时间：
2019-03
影响因子：
7.3
通讯作者：
Oviedo NJ
中科院分区：
文献类型：
--
作者：
Barghouth PG;Thiruvalluvan M;LeGro M;Oviedo NJ
老化和受损组织的忠实更新是生物体寿命的核心。干细胞（SCs）产生的细胞后代可以补充全身的成人组织，但随着时间的推移，这项任务越来越受到损害。sc介导的组织维持的年龄相关性下降是一个多因素事件，通常会影响基因组的完整性。在持续分裂的需求下，sc中存在DNA损伤，这对癌症等与年龄相关的疾病具有很大的风险。然而，在组织更新过程中，对具有基因组不稳定性和DNA损伤反应的SCs进行分析存在重大挑战。在这里，我们介绍了一种基于地中海扁形涡虫的替代实验系统，以解决在基因组不稳定性存在下sc介导的组织更新的有机水平研究。涡虫有丰富的SCs（新生细胞），维持高的细胞周转率，各种分子工具已经被开发来诱导DNA损伤和解剖新生细胞如何对这种应激源作出反应。地中海葡萄显示出高度的DNA修复机制和调节成年SCs的信号通路的进化保守性。我们描述了遗传诱导的dna损伤模型，并强调了在基因组不稳定的情况下影响细胞决定（如生存、增殖和死亡）的全身信号。我们还讨论了损伤修复过程中DNA损伤反应的转录组学变化，并提出DNA修复是组织再生的关键组成部分。在组织更新和再生过程中，利用涡虫进行的进一步研究将提供有关DNA损伤细胞存活和生长的调节机制的见解。
Faithful renewal of aging and damaged tissues is central to organismal lifespan. Stem cells (SCs) generate the cellular progeny that replenish adult tissues across the body but this task becomes increasingly compromised over time. The age related decline in SC-mediated tissue maintenance is a multifactorial event that commonly affects genome integrity. The presence of DNA damage in SCs that are under continuous demand to divide poses a great risk for age-related disorders such as cancer. However, performing analysis of SCs with genomic instability and the DNA damage response during tissue renewal present significant challenges. Here we introduce an alternative experimental system based on the planaria flatworm Schmidtea mediterranea to address at the organismal level studies intersecting SC-mediated tissue renewal in the presence of genomic instability. Planaria have abundant SCs (neoblasts) that maintain high rates of cellular turnover and a variety of molecular tools have been developed to induce DNA damage and dissect how neoblasts respond to this stressor. S. mediterranea displays high evolutionary conservation of DNA repair mechanisms and signaling pathways regulating adult SCs. We describe genetically induced-DNA damage models and highlight body-wide signals affecting cellular decisions such as survival, proliferation, and death in the presence of genomic instability. We also discuss transcriptomic changes in the DNA damage response during injury repair and propose DNA repair as key component of tissue regeneration. Additional studies using planaria will provide insights about mechanisms regulating survival and growth of cells with DNA damage during tissue renewal and regeneration.
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影响因子：
19
作者：
Ceccaldi R;Rondinelli B;D'Andrea AD
通讯作者：
D'Andrea AD
影响因子：
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影响因子：
11.2
作者：
Davis, JN;McCabe, MT;Day, ML
通讯作者：
Day, ML
影响因子：
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作者：
DIPERSIO, LP
通讯作者：
DIPERSIO, LP
影响因子：
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作者：
Altmeyer M;Messner S;Hassa PO;Fey M;Hottiger MO
通讯作者：
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