Title: Mammary stem cells: Novel markers and novel approaches to increase lactation efficiency Authors
Submitted to: Journal of Dairy Science
Publication Type: Abstract Only
Publication Acceptance Date: February 17, 2012
Publication Date: N/A
Technical Abstract: Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue repair. Accordingly, we and others have attempted to characterize and alter the function of bovine MaSC. Approaches used have included flow cytometry and in vitro cultivation to enrich for and characterize these cells. Recent data indicate that MaSC retain labeled DNA for extended periods. Relying on this long-term retention of bromodeoxyuridine-labeled DNA, we identified putative bovine MaSC and hypothesized that the label retaining epithelial cells (LREC) present in the basal layer of the mammary epithelium represent MaSC. As in other species, these cells were present in low abundance within mammary epithelium (< 1%) and were estrogen receptor-negative. We recently excised LREC and control cells from the mammary epithelium, using laser microdissection, and characterized their transcriptome by microarray analysis. Molecular profiles were consistent with the concept that LREC represent populations of MaSC and progenitor cells, that basal LREC are enriched for MaSC, and that LREC in suprabasal locations are enriched for committed progenitors. Analysis also provided novel candidate biomarkers for MaSC/progenitors. Potential biomarkers currently under investigation include NR5A2, NUP153, FNDC3B and HNF4A. Cells bearing these biomarkers are present in abundance and localization consistent with their utility as MaSC markers. We have attempted to modulate MaSC number in vivo and in vitro. Infusing a solution of xanthosine through the teat canal and into the mammary ductal network of prepubertal heifers and treatment of bovine mammary epithelial cells in vitro, increased the number of putative MaSC/progenitors. This was evidenced in vivo by an increase in the percentage of LREC and increased telomerase activity and in vitro by increased FNDC3B labeling and telomerase activity. The exciting possibility that stem cell expansion can influence milk production is under investigation.