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Tissue-Specific Stem Cells
Article first published online: 15 MAY 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 6, pages 1255–1264, June 2012
How to Cite
Thomas, E., Lee-Pullen, T., Rigby, P., Hartmann, P., Xu, J. and Zeps, N. (2012), Receptor Activator of NF-κB Ligand Promotes Proliferation of a Putative Mammary Stem Cell Unique to the Lactating Epithelium. STEM CELLS, 30: 1255–1264. doi: 10.1002/stem.1092
Author contributions: E.T.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; T.L.-P.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; P.R.: data analysis and interpretation and final approval of manuscript; P.H.: provision of study material and patients, financial support, and final approval of manuscript; J.X.: conception and design, provision of study material, data analysis and interpretation, and final approval of manuscript; N.Z.: manuscript writing and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS March 30, 2012.
- Issue published online: 15 MAY 2012
- Article first published online: 15 MAY 2012
- Accepted manuscript online: 30 MAR 2012 10:09AM EST
- Manuscript Received: 28 OCT 2011
- Manuscript Accepted: 25 FEB 2011
- Medela AG, Switzerland
- University of Western Australia, a facility funded by the University, State and Commonwealth Government
- Mammary gland;
- Stem cell;
- Progenitor cell;
- Receptor activator of NF-κB ligand
In mice, CD49fhi mammary stem cells (MaSCs) asymmetrically divide to generate CD49f+ committed progenitor cells that differentiate into CD49f− phenotypes of the milk-secreting tissue at the onset of pregnancy. We show CD49f+ primary mammary epithelial cells (PMECs) isolated from lactating tissue uniquely respond to pregnancy-associated hormones (PAH) compared with CD49f+ cells from nonlactating tissue. Differentiation of CD49f+ PMEC in extracellular matrix produces CD49f− luminal cells to form differentiated alveoli. The PAH prolactin and placental lactogen specifically stimulate division of CD49f− luminal cells, while receptor activator of nuclear factor (NF)-κB ligand (RANKL) specifically stimulates division of basal CD49f+ cells. In nondifferentiating conditions, we observed a greater proportion of multipotent self-renewing cells, and RANKL treatment activated the RANK pathway in these cultures. Furthermore, we observed the deposition of calcium nodules in a proportion of these cells. These data imply that a MaSC unique to the lactating breast exists in humans, which generates progeny with discrete lineages and distinct response to PAH. STEM CELLS2012;30:1255–1264