posters International Association for Breast Cancer Research 2014

Stem and progenitor cell division kinetics during postnatal mouse mammary gland development (#99)

Mona Shehata 1 , Rajshekhar Giraddi 1 , Mercedes Gallardo 2 , Maria A. Blasco 2 , Benjamin D. Simons 3
  1. Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, United Kingdom
  2. Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
  3. Cavendish Laboratory, University of Cambridge, Cambridge, United Kingdom

The cell division kinetics of mammary stem and progenitor cells is not known. To investigate this, we used quantitative stem and progenitor cell assays in combination with incorporation of synthetic nucleosides and sensitivity to the S-phase cytotoxin 5- fluorouracil to determine the cell division kinetics of the different mammary epithelial cell populations during postnatal mouse mammary development. Our results demonstrate that cell division within the mammary epithelium over the long-term is stochastic, but once a cell is recruited into the cell cycle in the estrus cycle, then cell division is repeated. Unexpectedly, most cell division in the adult virgin gland is restricted to a subpopulation of non-clonogenic luminal (NCL) cells that, paradoxically, have traditionally been perceived as being terminally differentiated. Our data also demonstrate that the NCL and the undifferentiated luminal progenitor population have cell division kinetics and telomere lengths that are compatible with these populations being largely maintained by their own restricted committed progenitors and not hierarchically organized. We also observe that transplantable stem cells have a cycling status that is linked to the estrus cycle, with these cells undergoing maximal cell division when progesterone levels are high.