Tao, Luweivan Bragt, Maaike P.A.Laudadio, ElizabethLi, Zhe2014-07-072014Tao, Luwei, Maaike P.A. van Bragt, Elizabeth Laudadio, and Zhe Li. 2014. “Lineage Tracing of Mammary Epithelial Cells Using Cell-Type-Specific Cre-Expressing Adenoviruses.” Stem Cell Reports 2 (6): 770-779. doi:10.1016/j.stemcr.2014.04.004. http://dx.doi.org/10.1016/j.stemcr.2014.04.004.2213-6711http://nrs.harvard.edu/urn-3:HUL.InstRepos:12406664Summary Lineage tracing using Cre/lox transgenic mice provides a powerful tool for studying normal mammary epithelial cell (MEC) development and the cellular origins of mammary tumors under physiological settings. However, generation of new transgenic mice for lineage-tracing purposes is often time consuming. Here, we report a lineage-tracing tool for MECs based on intraductal injection of lineage-specific Cre-expressing adenovirus (Ad-Cre). Using well-characterized promoters for Keratin 8 and Keratin 14, we generated lineage-specific Ad-Cre lines for luminal and basal MECs, respectively. By pulse-chase lineage tracing using these Ad-Cre lines, we showed that luminal and basal lineages are largely self-sustained and that IRS1 and IRS2 are essential for maintaining the basal lineage; we also showed that heterogeneous mammary tumors can be induced from luminal MECs in mice carrying the Etv6-NTRK3 fusion gene. Overall, we validated the Ad-Cre system as a promising and efficient tool for fate mapping of normal and malignant cells in adult tissues.en-USJournal Article2014-07-0710.1016/j.stemcr.2014.04.004