The mammary epithelium is formed by luminal cells, which produce and transport milk and myoepithelial cells. Previous transplantation studies suggested that the several lineages that constitute and regenerate the mammary epithelium arise from multipotent mammary stem cells. Blanpain and colleagues (http://dx.doi.org/10.1038/nature10573) use a lineage-tracing approach in the mouse to show that although multipotent stem cells exist in the neonatal mammary gland, the postnatal mammary gland is maintained by long-lived unipotent stem cells that are able to expand the gland at puberty and renew it during pregnancy. They induced the expression of fluorescently labelled markers previously associated with gland stem cells and followed their contribution to the gland. Multipotent embryonic K14-expressing progenitors were confirmed to exist at birth, but it was found that later in life K14-expressing cells contribute only to the myoepithelial lineage. K8-labelled cells instead defined the luminal stem cells. To reconcile their results with previous studies indicating the presence of bipotent progenitors within the adult mammary gland, the authors transplanted isolated fluorescently labelled K14 or K8 cells, singly or in combination. They found that in conditions where luminal cells are few or absent, rare K14 cells adopt a luminal fate.

Uncovering these distinct long-lived stem cells in the mammary gland should help defining the cells at the origin of breast tumours.