涡虫 p53 同源物调节成体干细胞谱系中的增殖和自我更新。
A planarian p53 homolog regulates proliferation and self-renewal in adult stem cell lineages.
机构信息
Department of Neurobiology and Anatomy, Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84132, USA.
出版信息
Development. 2010 Jan;137(2):213-21. doi: 10.1242/dev.044297.
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.
成体干细胞的功能和肿瘤抑制基因的功能已知有交集。然而，肿瘤抑制因子在成体干细胞产生的谱系中是如何发挥作用的，目前还不清楚。由于淡水涡虫拥有大量可以在体内进行操作和研究的干细胞，因此它是一个理想的系统，可以用来研究这些问题。在这里，我们主要关注肿瘤抑制因子 p53，到目前为止，在任何研究过的无脊椎动物中，还没有发现其同源物在干细胞生物学中有任何已知作用。涡虫只有一个 p53 家族成员 Smed-p53，它主要在新生成的干细胞后代中表达。当 Smed-p53 被 RNAi 靶向时，干细胞群体以牺牲后代为代价增加，导致过度增殖。然而，最终干细胞群体无法自我更新。我们的结果表明，在脊椎动物之前，一种祖先的 p53 样分子已经在干细胞增殖控制和自我更新中发挥作用。
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