SCA-1 Labels a Subset of Estrogen-Responsive Bipotential Repopulating Cells within the CD24(+) CD49f(hi) Mammary Stem Cell-Enriched Compartment

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Dall, GV; Vieusseux, JL; Korach, KS; Arao, Y; Hewitt, SC; Hamilton, KJ; Dzierzak, E; Boon, WC; Simpson, ER; Ramsay, RG; ...Date
2017-02-14Source Title
Stem Cell ReportsPublisher
CELL PRESSUniversity of Melbourne Author/s
Anderson, Robin; Ramsay, Robert; Britt, Kara; Boon, Wah Chin; Risbridger, GailAffiliation
Sir Peter MacCallum Department of OncologySchool of BioSciences
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Dall, G. V., Vieusseux, J. L., Korach, K. S., Arao, Y., Hewitt, S. C., Hamilton, K. J., Dzierzak, E., Boon, W. C., Simpson, E. R., Ramsay, R. G., Stein, T., Morris, J. S., Anderson, R. L., Risbridger, G. P. & Britt, K. L. (2017). SCA-1 Labels a Subset of Estrogen-Responsive Bipotential Repopulating Cells within the CD24(+) CD49f(hi) Mammary Stem Cell-Enriched Compartment. STEM CELL REPORTS, 8 (2), pp.417-431. https://doi.org/10.1016/j.stemcr.2016.12.022.Access Status
Open AccessAbstract
Estrogen stimulates breast development during puberty and mammary tumors in adulthood through estrogen receptor-α (ERα). These effects are proposed to occur via ERα+ luminal cells and not the mammary stem cells (MaSCs) that are ERαneg. Since ERα+ luminal cells express stem cell antigen-1 (SCA-1), we sought to determine if SCA-1 could define an ERα+ subset of EpCAM+/CD24+/CD49fhi MaSCs. We show that the MaSC population has a distinct SCA-1+ population that is abundant in pre-pubertal mammary glands. The SCA-1+ MaSCs have less stem cell markers and less in vivo repopulating activity than their SCA-1neg counterparts. However, they express ERα and specifically enter the cell cycle at puberty. Using estrogen-deficient aromatase knockouts (ArKO), we showed that the SCA-1+ MaSC could be directly modulated by estrogen supplementation. Thus, SCA-1 enriches for an ERα+, estrogen-sensitive subpopulation within the CD24+/CD49fhi MaSC population that may be responsible for the hormonal sensitivity of the developing mammary gland.
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