Lineage tracing of mammary epithelial cells using cell-type-specific cre-expressing adenoviruses

Stem Cell Reports. 2014 May 9;2(6):770-9. doi: 10.1016/j.stemcr.2014.04.004. eCollection 2014 Jun 3.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism*
  • Female
  • Insulin Receptor Substrate Proteins / genetics
  • Keratin-14 / genetics
  • Keratin-8 / genetics
  • Mammary Glands, Animal / cytology*
  • Mice
  • Mice, Transgenic
  • Oncogene Proteins, Fusion / genetics

Substances

  • ETV6-NTRK3 fusion protein, mouse
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • Irs2 protein, mouse
  • Keratin-14
  • Keratin-8
  • Oncogene Proteins, Fusion