s-SHIP promoter expression marks activated stem cells in developing mouse mammary tissue.

Publication Type:

Journal Article

Source:

Genes & development, Volume 24, Issue 17, p.1882-92 (2010)

Keywords:

2010, Animals, Basic Sciences Division, Breast Neoplasms, Cell Differentiation, Center-Authored Paper, Comparative Medicine Core Facility, Female, Flow Cytometry Core Facility, Gene Expression Regulation, Developmental, Gene Expression Regulation, Neoplastic, Green Fluorescent Proteins, Mammary Glands, Animal, MICE, Mice, Transgenic, Phosphoric Monoester Hydrolases, PREGNANCY, Promoter Regions, Genetic, Scientific Imaging Core Facility, Shared Resources, Stem Cells

Abstract:

Mammary stem cells (MaSCs) play critical roles in normal development and perhaps tumorigenesis of the mammary gland. Using combined cell markers, adult MaSCs have been enriched in a basal cell population, but the exact identity of MaSCs remains unknown. We used the s-SHIP promoter to tag presumptive stem cells with GFP in the embryos of a transgenic mouse model. Here we show, in postnatal mammary gland development, that GFP(+) cap cells in puberty and basal alveolar bud cells in pregnancy each exhibit self-renewal and regenerative capabilities for all mammary epithelial cells of a new functional mammary gland upon transplantation. Single GFP(+) cells can regenerate the mammary epithelial network. GFP(+) mammary epithelial cells are p63(+), CD24(mod), CD49f(high), and CD29(high); are actively proliferating; and express s-SHIP mRNA. Overall, our results identify the activated MaSC population in vivo at the forefront of rapidly developing terminal end buds (puberty) and alveolar buds (pregnancy) in the mammary gland. In addition, GFP(+) basal cells are expanded in MMTV-Wnt1 breast tumors but not in ErbB2 tumors. These results enable MaSC in situ identification and isolation via a consistent single parameter using a new mouse model with applications for further analyses of normal and potential cancer stem cells.