Regional signals in the planarian body guide stem cell fate in the presence of genomic instability
Regional signals in the planarian body guide stem cell fate in the presence of genomic instability
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DOI：
10.1242/dev.131318
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发表时间：
2016-05-15
期刊：
影响因子：
4.6
通讯作者：
Oviedo, Nestor J.
中科院分区：
文献类型：
--
作者：
Peiris, T. Harshani;Ramirez, Daniel;Oviedo, Nestor J.
细胞的命运决定受其在成人体内的地形位置的影响。例如，组织修复和肿瘤生长在成年动物的前部比后部更大。然而，这些区域差异的分子基础是未知的。我们发现，在Rad51的rna干扰下，成年涡虫体内的同源重组被系统性破坏时，存在一个区域开关。Rad51敲低会增加全身DNA双链断裂（DSBs），但干细胞的反应不同，取决于它们在前后轴上的位置。在广泛存在dsb的情况下，身体前部的细胞抵抗死亡，而后部的细胞则发生凋亡。此外，我们发现，在脑组织存在的情况下，DNA损伤细胞的增殖被诱导，视网膜母细胞瘤通路使dsb细胞过度增殖，同时满足组织生长和修复的需要。我们的研究结果暗示自主和非自主机制都是成人体内区域细胞行为和细胞转化的关键介质。
Cellular fate decisions are influenced by their topographical location in the adult body. For instance, tissue repair and neoplastic growth are greater in anterior than in posterior regions of adult animals. However, the molecular underpinnings of these regional differences are unknown. We identified a regional switch in the adult planarian body upon systemic disruption of homologous recombination with RNA-interference of Rad51. Rad51 knockdown increases DNA double-strand breaks (DSBs) throughout the body, but stem cells react differently depending on their location along the anteroposterior axis. In the presence of extensive DSBs, cells in the anterior part of the body resist death, whereas cells in the posterior region undergo apoptosis. Furthermore, we found that proliferation of cells with DNA damage is induced in the presence of brain tissue and that the retinoblastoma pathway enables overproliferation of cells with DSBs while attending to the demands of tissue growth and repair. Our results implicate both autonomous and non-autonomous mechanisms as key mediators of regional cell behavior and cellular transformation in the adult body.