Genetic lineage tracing unravels cell fate and plasticity in development, tissue homeostasis, and diseases. However, it remains technically challenging to trace temporary or transient cell fate, such as epithelial-to-mesenchymal transition (EMT) in tumor metastasis. Here, we generated a genetic fate-mapping system for temporally seamless tracing of transient cell fate. Highlighting its immediate application, we used it to study EMT gene activity from the local primary tumor to a distant metastatic site in vivo. In a spontaneous breast-to-lung metastasis model, we found that primary tumor cells activated vimentin and N-cadherin in situ, but only N-cadherin was activated and functionally required during metastasis. Tumor cells that have ever expressed N-cadherin constituted the majority of metastases in lungs, and functional deletion of N-cad significantly reduced metastasis. The seamless genetic recording system described here provides an alternative way for understanding transient cell fate and plasticity in biological processes.

遗传谱系追踪揭示了发育，组织稳态和疾病中的细胞命运和可塑性。然而，在肿瘤转移中追踪临时或短暂的细胞命运（例如上皮到间质转化（EMT））在技术上仍然具有挑战性。在这里，我们生成了一个遗传命运映射系统，用于瞬时无缝地追踪瞬时细胞命运。为了突出其直接应用，我们使用它来研究从体内原发性肿瘤到远处转移部位的EMT基因活性。在自发的乳房到肺转移模型中，我们发现原发性肿瘤细胞原位激活波形蛋白和N-钙粘蛋白，但只有N-钙粘着蛋白在转移过程中被激活并需要功能。曾经表达过N-钙粘着蛋白的肿瘤细胞构成了肺部的大部分转移灶，而N-cad的功能性缺失大大降低了转移灶。这里描述的无缝基因记录系统为理解瞬时细胞命运和生物过程中的可塑性提供了另一种方法。