Molecular signature of the putative stem/progenitor cells committed to the development of the bovine mammary gland at puberty

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 from the related epithelial hierarchy. Using cell phenotyping and sorting, we highlighted four cell sub-populations within the bovine mammary gland at puberty. The CD49(f)(high)CD24(neg) cells expressing CD10, KRT14, vimentin and PROCR corresponded to cells committed to the basal lineage. The CD49(f)(low) sub-population contained two cell subsets (CD49(f)(low)CD24(neg) and CD49(f)(low)CD24(pos)). Both subsets expressed hormone receptors including ER, PR and PRLR, as well as ALDH1 activity but only the CD49(f)(low)CD24(pos) subset expressed ELF5. These data indicated that the CD49(f)(low) sub-population is mainly composed of cells displaying a luminal phenotype and that this population comprises two luminal cell subsets, namely the CD24(neg) and CD24(pos) cells, likely committed to ductal and alveolar lineage, respectively. The putative mammary stem cell (MaSC) fraction was recovered in the CD49(f)(high)CD24(pos) sub-population which were shown to form mammospheres in vitro. These cells differentially expressed CD10, KRT14 and KRT7, suggesting the existence of several putative MaSC sub-fractions. In-depth characterization of these epithelial sub-populations provides new insights into the bovine mammary epithelial cell lineage and suggests a common developmental lineage in mammals.