Abstract
BackgroundMammary stem cells are critical for growth and maintenance of the mammary gland and therefore are of considerable interest for improving productivity and efficiency of dairy animals. Xanthosine treatment has been demonstrated to promote expansion of putative mammary stem cells in vivo, and hepatic and hair follicle stem cells in vitro. In the latter, xanthosine promoted the symmetrical division of hepatic and hair follicle stem cells. The objective of this study was to determine if treating primary cultures of bovine mammary epithelial cells (MEC) with xanthosine increases the stem/progenitor cell population by promoting symmetrical division of mammary stem cells.ResultsIn vitro treatment with xanthosine increased the population of MEC during the exponential phase of cell growth, reducing the doubling time from 86 h in control cultures to 60 h in xanthosine-treated cultures. The bromodeoxyuridine (BrdU) labeling index and the proportion of MEC in S-phase both were increased by xanthosine treatment, indicating that increased cell accretion was due to increased cell proliferation. Analysis of daughter-pairs indicated that xanthosine promoted a shift from asymmetric to symmetric cell division. Moreover, the 30 % increase in symmetric cell division was concomitant with an increase in the proportion of MEC that were positive for a putative stem cell marker (FNDC3B) and a trend toward increased telomerase activity. These results suggest that xanthosine treatment in vitro can increase cell proliferation, promote symmetric cell division and enhance stem/progenitor cell activity.ConclusionsXanthosine treatment increased the proliferation rate of bovine MEC in vitro. This was likely to be mediated by an increase in the proportion of stem/progenitor cells in the MEC population due to promotion of symmetrical stem cell division by xanthosine.
Highlights
Mammary stem cells are critical for growth and maintenance of the mammary gland and are of considerable interest for improving productivity and efficiency of dairy animals
Growth kinetics and effect of xanthosine The initial experiment evaluated the impact of xanthosine on growth of primary bovine mammary epithelial cells (MEC)
FNDC3B is a potential marker of bovine mammary stem and progenitor cells that we recently identified by microarray analysis of label-retaining epithelial cells (LREC), which were excised by laser microdissection from cryosections of mammary tissue [11]
Summary
Mammary stem cells are critical for growth and maintenance of the mammary gland and are of considerable interest for improving productivity and efficiency of dairy animals. Xanthosine treatment has been demonstrated to promote expansion of putative mammary stem cells in vivo, and hepatic and hair follicle stem cells in vitro. In the latter, xanthosine promoted the symmetrical division of hepatic and hair follicle stem cells. The objective of this study was to determine if treating primary cultures of bovine mammary epithelial cells (MEC) with xanthosine increases the stem/progenitor cell population by promoting symmetrical division of mammary stem cells. Mammary stem cells (MaSC) are somatic stem cells that provide for the lineage of mammary epithelial cells They are of considerable interest to developmental biologists, agricultural scientists and cancer researchers. Information gained will potentially broaden our knowledge of human mammary epithelial cells and stem cells
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