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Title: CELL PROLIFERATION IN BOVINE MAMMARY EPITHELIUM: IDENTIFICATION OF THE PRIMARY PROLIFERATIVE CELL POPULATION.

Author
item Capuco, Anthony
item ELLIS, STEVEN - 1265-45-00

Submitted to: Tissue and Cell
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/15/2002
Publication Date: 3/15/2002
Citation: CAPUCO, A.V., ELLIS, S.E. CELL PROLIFERATION IN BOVINE MAMMARY EPITHELIUM: IDENTIFICATION OF THE PRIMARY PROLIFERATIVE CELL POPULATION. TISSUE AND CELL. vol. 34(3), pp. 155-163, 2002.

Interpretive Summary: A histological evaluation of prepubertal mammary gland was performed to identify potential mammary stem cell populations in the bovine mammary gland. Three categories of cells could be distinguished: light, intermediate and dark staining cells. Light staining cells accounted for 10% of the total population of mammary epithelial cells but comprised 50% of the proliferating cells. Light and intermediate cells together account for greater than 90% of the proliferating mammary epithelial cells. These data provide quantitative support for the hypothesis that lightly staining mammary epithelial cells are the primary proliferative population and suggest that the intermediately staining provide a population of actively proliferating daughter cells. This information will aid in the development of treatments to improve ruminant mammary development and to maintain the population milk producing cells during lactation.

Technical Abstract: Isolation and characterization of mammary stem cells would be a boon for developmental, clinical, and agricultural research. Unfortunately, no positive markers for mammary stem cells have yet been identified. Histologic analyses indicate that a pale staining cell population present in mammary parenchyma may function as mammary stem cells. To investigate this possibility, we have performed an analysis of mammary epithelial cell proliferation in outer, medial, and cisternal parenchymal zones of prepubertal bromodeoxyuridine-injected (BrdU) Holstein heifers at 2, 5, and 8 months of age. We observed light, dark, and intermediate staining cells in histologic sections stained with basic fuschin and azure II. Light cells comprised only 10% of the total parenchymal cell population but accounted for 50% of the cell proliferation. Intermediate cells comprised 60% of the total cell population and accounted for 43% of proliferating cells. Dark cells comprised 30% of the total parenchymal cell population but only 7% of cell proliferation. While the distribution of BrdU+ cells across basal, embedded, and lumenal parenchymal cell layers was correlated with the fraction of the total parenchymal cell population present in each layer (r = 0.99), the proportion of mitotic cells observed in the basal cell layer was only half of what would be predicted by the BrdU labeling data. This observation suggests that some basal cells either arrest in G2 or migrate into the suprabasal epithelial layers before undergoing mitosis. Our data provides the first quantitative support for the concept that lightly staining mammary epithelial cells are the primary proliferative cell population and provide critical insight into the cell types and processes involved in ruminant mammogenesis.