A planarian p53 homolog regulates proliferation and self-renewal in adult stem cell lineages
A planarian p53 homolog regulates proliferation and self-renewal in adult stem cell lineages
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DOI：
10.1242/dev.044297
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发表时间：
2010-01-15
期刊：
影响因子：
4.6
通讯作者：
Alvarado, Alejandro Sanchez
中科院分区：
文献类型：
--
作者：
Pearson, Bret J.;Alvarado, Alejandro Sanchez
众所周知，成体干细胞和肿瘤抑制基因的功能是交叉的。然而，肿瘤抑制因子何时以及如何在成体干细胞产生的谱系中起作用尚不清楚。淡水涡虫拥有大量可在体内操作和研究的干细胞，是研究这些问题的理想系统。在这里，我们关注肿瘤抑制因子p53，其同源物在任何无脊椎动物的干细胞生物学中迄今为止还没有已知的作用。涡虫有一个单一的p53家族成员，smad -p53，主要在新制造的干细胞后代中表达。当Smed-p53被RNAi靶向时，干细胞群的增加以牺牲后代为代价，导致过度增殖。然而，最终干细胞群不能自我更新。我们的研究结果表明，在脊椎动物出现之前，一种类似p53的祖先分子已经在干细胞增殖控制和自我更新中发挥了作用。
The functions of adult stem cells and tumor suppressor genes are known to intersect. However, when and how tumor suppressors function in the lineages produced by adult stem cells is unknown. With a large population of stem cells that can be manipulated and studied in vivo, the freshwater planarian is an ideal system with which to investigate these questions. Here, we focus on the tumor suppressor p53, homologs of which have no known role in stem cell biology in any invertebrate examined thus far. Planaria have a single p53 family member, Smed-p53, which is predominantly expressed in newly made stem cell progeny. When Smed-p53 is targeted by RNAi, the stem cell population increases at the expense of progeny, resulting in hyper-proliferation. However, ultimately the stem cell population fails to self-renew. Our results suggest that prior to the vertebrates, an ancestral p53-like molecule already had functions in stem cell proliferation control and self-renewal.