Howard Hughes Medical Institute, MIT Biology, Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Cell Stem Cell. 2012 Mar 2;10(3):299-311. doi: 10.1016/j.stem.2012.01.016.
Pluripotency is a central, well-studied feature of embryonic development, but the role of pluripotent cell regulation in somatic tissue regeneration remains poorly understood. In planarians, regeneration of entire animals from tissue fragments is promoted by the activity of adult pluripotent stem cells (cNeoblasts). We utilized transcriptional profiling to identify planarian genes expressed in adult proliferating, regenerative cells (neoblasts). We also developed quantitative clonal analysis methods for expansion and differentiation of cNeoblast descendants that, together with RNAi, revealed gene roles in stem cell biology. Genes encoding two zinc finger proteins, Vasa, a LIM domain protein, Sox and Jun-like transcription factors, two candidate RNA-binding proteins, a Setd8-like protein, and PRC2 (Polycomb) were required for proliferative expansion and/or differentiation of cNeoblast-derived clones. These findings suggest that planarian stem cells utilize molecular mechanisms found in germ cells and other pluripotent cell types and identify genetic regulators of the planarian stem cell system.
多能性是胚胎发育的一个中心特征，也是研究热点，但多能细胞调控在体组织再生中的作用仍知之甚少。在水螅中，组织碎片能再生出完整的动物，这一过程依赖于成体多能干细胞（cNeoblasts）的活性。我们利用转录组学方法，鉴定了成年增殖性、再生性细胞（neoblasts）中表达的水螅基因。我们还开发了用于 cNeoblast 后代扩增和分化的定量克隆分析方法，与 RNAi 结合使用，揭示了这些基因在干细胞生物学中的作用。编码两个锌指蛋白（Vasa、LIM 结构域蛋白 Sox 和 Jun 样转录因子）、两个候选 RNA 结合蛋白、一个 Setd8 样蛋白和 PRC2（Polycomb）的基因，对于 cNeoblast 衍生克隆的增殖扩增和/或分化是必需的。这些发现表明，水螅干细胞利用了在生殖细胞和其他多能细胞类型中发现的分子机制，并确定了水螅干细胞系统的遗传调控因子。
