A European team of scientists has identified new populations of breast stem cells that guarantee the creation, expansion and maintenance of the diverse cell lineages of the mammary gland during pregnancy and throughout life. Presented in the journal Nature, the study was funded in part by CANCERSTEM ("Stem cells in epithelial cancer initiation and growth"), a project that received a European Research Council Starting Grant worth EUR 1.6 million under the EU's Seventh Framework Programme (FP7).
Biologists have long been keen to determine which stem cells are responsible for tissue morphogenesis and regeneration during the two stages in which the mammary gland expands most significantly: puberty and pregnancy.
The team of researchers from the Institut de Recherche Interdisciplinaire en Biologie Humaine et Molécular (IRIBHM) at the Université libre de Bruxelles in Belgium has identified two distinct stem cell types that together form cell lineages that maintain the mammary gland: luminal stem cells that differentiate into either ductal or milk-producing cells, secreting water and nutrients required to ensure the survival of young mammalian offspring; and stem cells giving rise to myoepithelial cells that through their contraction guide the circulation of the milk throughout the ductal tree toward the nipple.
Led by Alexandra Van Keymeulen of the Université libre de Bruxelles, the team used a novel and sophisticated genetic lineage-tracing approach to fluorescently mark the different cell types of the mammary gland and follow the fate of fluorescent-marked cells over time. Doing so allowed them to precisely define the cellular hierarchy of the mammary gland during physiological conditions.
Both myoepithelial and luminal lineages have long-lived unipotent stem cells that demonstrate extensive renewing capacities. These stem cells can expand during morphogenesis and during a number of pregnancy cycles.
'We were all very surprised and excited when we discovered that the mammary glands are maintained by two classes of unipotent stem cells ensuring the renewal and differentiation of their respective lineages, rather than by multipotent stem cells,' says Dr Van Keymeulen, lead author of the study. 'These findings radically change our understanding of the regenerative potential of the mammary gland during physiological conditions.'
Commenting on the results of the study, senior author Cédric Blanpain of the Université libre de Bruxelles says: 'These new findings will be extremely important for those studying development, stem cells and mammary glands but also opens new avenues to uncover the cells at the origin of the different subtypes of breast cancers, a very important and unanswered question.'