In situ identification of bipotent stem cells in the mammary gland

The mammary epithelium undergoes profound morphogenetic changes during development. Architecturally, it comprises two primary lineages, the inner luminal and outer myoepithelial cell layers. Two opposing concepts on the nature of mammary stem cells (MaSCs) in the postnatal gland have emerged. One model, based on classical transplantation assays, postulates that bipotent MaSCs have a key role in coordinating ductal epithelial expansion and maintenance in the adult gland, whereas the second model proposes that only unipotent MaSCs identified by lineage tracing contribute to these processes. Through clonal cell-fate mapping studies using a stochastic multicolour cre reporter combined with a new three-dimensional imaging strategy, we provide evidence for the existence of bipotent MaSCs as well as distinct long-lived progenitor cells. The cellular dynamics at different developmental stages support a model in which both stem and progenitor cells drive morphogenesis during puberty, whereas bipotent MaSCs coordinate ductal homeostasis and remodelling of the mouse adult gland. Through the use of a novel three-dimensional imaging technique, used in conjunction with a multicolour reporter that allows lineage tracing and cell tracking of entire mammary ducts in vivo , bipotent stem cells are shown to have a central role in both puberty and long-term maintenance; in addition, long-lived luminal progenitor cells with a prominent role in ductal expansion are identified. Active bipotent stem cells in the mammary gland The respective roles of bipotent and unipotent stem cells in the mammalian mammary gland are a focus of much current research. Jane Visvader and colleagues have developed a three-dimensional imaging technique to use in combination with a stochastic multicolour reporter that allows lineage tracing at a clonal level and cell tracking in vivo of entire mammary ducts. Using this approach the authors show that bipotent mammary stem cells have a central role in the morphogenesis of the gland during puberty and in long-term maintenance. They also identify long-lived luminal progenitor cells in situ that have a prominent role in ductal expansion.