title: Lineage tracing of mammary epithelial cells using cell-type-specific cre-expressing adenoviruses.
abstract: 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.
authors.affiliation: Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA ; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Luwei
authors.initials: L
authors.lastname: Tao
authors.affiliation: Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA ; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Maaike P A
authors.initials: MP
authors.lastname: van Bragt
authors.affiliation: Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA ; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Laudadio
authors.affiliation: Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA ; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D053547:Keratin-14 / Q000235:genetics; D053533:Keratin-8 / Q000235:genetics; D008321:Mammary Glands, Animal / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D055504:Insulin Receptor Substrate Proteins; D053547:Keratin-14; D053533:Keratin-8; D015514:Oncogene Proteins, Fusion; C526167:ETV6-NTRK3 fusion protein, mouse; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein; C526295:Irs1 protein, mouse; C526298:Irs2 protein, mouse