Somatic models of tissue pathology commonly utilise induction of gene specific mutations in mice mediated by spatiotemporal regulation of Cre recombinase. Subsequent investigation of the onset and development of disease can be limited by the inability to track changing cellular behaviours over time. Here a lineage tracing approach based on ligand dependent activation of Dre recombinase that can be employed independently of Cre is described. The clonal biology of intestinal epithelium following Cre-mediated stabilisation of ß-catenin reveals that within tumours many new clones rapidly become extinct. Surviving clones show accelerated population of tumour glands compared to normal intestinal crypts but in a non-uniform manner indicating that intra-tumour glands follow heterogeneous dynamics. In tumour adjacent epithelium clone sizes are smaller than in the background epithelium as a whole. This suggests a zone of around 5 crypt diameters within which clone expansion is inhibited by tumours and that may facilitate their growth.

中文翻译：

---

通过 Dre 介导的谱系追踪鉴定肠道肿瘤内部和邻近的克隆动力学的异质性。

组织病理学的体细胞模型通常利用 Cre 重组酶的时空调节介导的小鼠基因特异性突变的诱导。由于无法跟踪随时间变化的细胞行为，对疾病发生和发展的后续研究可能受到限制。这里描述了一种基于 Dre 重组酶的配体依赖性激活的谱系追踪方法，该方法可以独立于 Cre 来使用。Cre 介导的 β-连环蛋白稳定后肠上皮的克隆生物学表明，肿瘤内许多新克隆迅速灭绝。与正常肠隐窝相比，存活的克隆显示肿瘤腺体的数量加速，但以不均匀的方式表明肿瘤内腺体遵循异质动态。在肿瘤中，邻近上皮克隆的尺寸总体上小于背景上皮中的尺寸。这表明有一个大约 5 个隐窝直径的区域，在该区域内克隆扩张受到肿瘤的抑制，并且可能促进它们的生长。