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SCA-1 Labels a Subset of Estrogen-Responsive Bipotential Repopulating Cells within the CD24 + CD49f hi Mammary Stem Cell-Enriched Compartment
,
Yukitomo Arao,
Sylvia C. Hewitt,
Katherine J. Hamilton,
Elaine Dzierzak,
Wah Chin Boon,
Evan R. Simpson,
Robert G. Ramsay,
Torsten Stein,
Joanne S. Morris,
Robin L. Anderson,
Gail P. Risbridger,
Kara L. Britt
Abstract
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.