Bovine mammary gland development: new insights into the epithelial hierarchy

Milk production is highly dependent on the extensive development of the mammary epithelium, which occurs during puberty. It is therefore essential to distinguish the epithelial cells committed to development during this key stage from the related epithelial hierarchy. Using cell phenotyping and sorting, we highlighted three sub-populations that we assume to be progenitors. The CD49 f high CD24 neg cells expressing KRT14 , vimentin and PROCR corresponded to basal progenitors whereas the CD49 f low CD24 neg cells expressing luminal KRT, progesterone and prolactin receptors, were of luminal lineage. The CD49 f low CD24 pos cells had features of a dual lineage, with luminal and basal characteristics (CD10, ALDH1 and KRT7 expression) and were considered to be early common (bipotent) progenitors. The mammary stem cell (MaSC) fraction was recovered in a fourth sub-population of CD49 f high CD24 pos cells that expressed CD10/ KRT14 and KRT7 . The differential ALDH1 activities observed within the MaSC fraction allowed to discriminate between two states: quiescent MaSCs and lineage-restricted “activated” MaSCs. The in-depth characterization of these epithelial sub-populations provides new insights into the epithelial cell hierarchy in the bovine mammary gland and suggests a common developmental hierarchy in mammals.