Distinct types of stem cells contribute to mammary gland development and maintenance

In a study published in Nature, researchers lead by Cédric Blanpain, MD/PhD, FNRS/FRS researcher and Welbio investigator at the IRIBHM (Faculty of Medicine), Université libre de Bruxelles, Belgium, identify novel classes of breast stem cells that ensure the development and expansion of the different cell lineages of the mammary gland during pregnancy.

The mammary gland expands considerably during puberty and pregnancy, during which it differentiated into milk-producing cells. Two different cell types formed the mammary gland : the myoepithelial cells and luminal cells, which can differentiate either into ductal cells or milk-producing cells. Whereas ductal and milk-producing cells secrete the water and nutriments essential for the survival of young mammalian offspring, the myoepithelial cells, through their contraction, guide the circulation of the milk throughout the ductal tree toward the nipple.

To precisely define the cellular hierarchy of mammary gland during physiological conditions, A. Van Keymeulen and colleagues used a novel state of the art genetic lineage tracing approach to fluorescently mark the different cell types of the mammary gland and follow the fate of fluorescent marked cells overtime. The researchers found that both luminal and myoepithelial lineages contain long lived unipotent stem cells which present extensive renewing capacities, as demonstrated by their ability to expand during morphogenesis and undergo massive expansion during several cycles of pregnancy. "We were all very surprised and excited when we discovered that the mammary glands are maintained by two classes of unipotent stem ensuring the renewal and differentiation of their respective lineages rather than by multipotent stem cells. These findings radically change our understanding of the regenerative potential of the mammary gland during physiological condition" said Alexandra Van Keymeulen, PhD and co-first author of this study. "This new findings will be extremely important for those studying development, stem cells and mammary gland 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" said Cédric Blanpain, the senior and corresponding author of the Nature paper.

In conclusion, this new study, published in the online early edition of Nature, identifies new stem cell populations in the breast tissue that ensure the development and the maintenance of the mammary gland throughout life.

This work was supported by the FNRS, TELEVIE, the "programme d'excellence" CIBLES of the Wallonia Region, a research grant from the Fondation Contre le Cancer, the ULB Fondation, the fond Gaston Ithier. Cédric Blanpain is an investigator of Welbio and is supported by a starting grant of the European Research Council (ERC) and the EMBO Young Investigator Program.