Lineage-Biased Stem Cells Maintain Estrogen-Receptor-Positive and -Negative Mouse Mammary Luminal Lineages

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Chunhui Wang, John R. Christin, Maja H. Oktay, Wenjun Guo
Delineating the mammary differentiation hierarchy is important for the study of mammary gland development and tumorigenesis. Mammary luminal cells are considered a major origin of human breast cancers. However, how estrogen-receptor-positive (ER⁺) and ER⁻ luminal cells are developed and maintained remains poorly understood. The prevailing model suggests that a common stem/progenitor cell generates both cell types. Through genetic lineage tracing in mice, we find that SOX9-expressing cells specifically contribute to the development and maintenance of ER⁻ luminal cells and, to a lesser degree, basal cells. In parallel, PROM1-expressing cells give rise only to ER⁺ luminal cells. Both SOX9⁺ and PROM1⁺ cells specifically sustain their respective lineages even after pregnancy-caused tissue remodeling or serial transplantation, demonstrating characteristic properties of long-term repopulating stem cells. Thus, our data reveal that mouse mammary ER⁺ and ER⁻ luminal cells are two independent lineages that are maintained by distinct stem cells, providing a revised mammary epithelial cell hierarchy.

Graphical abstract

Teaser

Wang et al. discovered two distinct lineage-biased stem cells in the mouse mammary gland: one contributes to the development of estrogen-receptor-negative luminal cells, and the other maintains the development of estrogen-receptor-positive luminal cells. These findings provide a new framework for studying mammary differentiation and breast cancer etiology.


http://ift.tt/2n5XxFu