Title: In vitro expansion of the mammary stem/progenitor cell population by xanthosinetreatment Authors
Submitted to: BioMed Central (BMC) Cell Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 22, 2012
Publication Date: June 1, 2012
Repository URL: http://hdl.handle.net/10113/42290
Citation: Choudhary, R.K., Capuco, A.V. 2012. In vitro expansion of the mammary stem/progenitor cell population by xanthosinetreatment. BioMed Central (BMC) Cell Biology. 13:14. Interpretive Summary: Mammary stem cells (MaSC) account for the cell lineages of the mammary secretory tissue and provide for mammary growth, development and tissue maintenance. The ability to modulate MaSC proliferation can be utilized to increase the efficiency of dairy production. We cultured bovine mammary epithelial cells and tested the ability of xanthosine, a natural nucleoside, to increase the proliferation of these cells. Stem cells can undergo symmetrical division, in which the two daughter progeny are both stem cells, or asymmetric division in which one daughter cell is a stem cell and the other a differentiated cell. Xanthosine treatment increased the proliferation rate of bovine MEC in vitro. This appeared to be mediated by an increase in the proportion of mammary stem cells in the culture, due to the promotion of symmetrical stem cell division.
Technical Abstract: Background: Mammary stem cells are critical for growth and maintenance of the mammary gland and therefore of considerable interest for improving productivity and efficiency of dairy animals. Xanthosine (Xs) treatment has been demonstrated to promote expansion of putative mammary stem cells in vivo and hepatic stem cells in vitro. In the latter case, Xs promoted the symmetrical division of hepatic stem cells. The objective of this study was to determine if treating primary cultures of bovine mammary epithelial cells (MEC) with Xs increases the stem/progenitor cell population by promoting symmetrical division of mammary stem cells. Results: In vitro treatment with Xs increased the population of bovine MEC during the exponential phase of cell growth, reducing the doubling time from 86 h in control cultures to 60 h in Xs-treated cultures. The bromodeoxyuridine (BrdU) labeling index and the proportion of MEC in S-phase both were increased by Xs treatment, indicating that increased cell accretion was due to increased cell proliferation. Analysis of daughter-pairs indicated that Xs 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 Xs treatment in vitro can increase cell proliferation, promote symmetric cell division and enhance stem/progenitor cell activity. Conclusions: Xanthosine treatment increased the proliferation rate of bovine MEC in vitro. This appeared 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 Xs.