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

Genevieve V Dall, Jessica L Vieusseux, Kenneth S Korach, 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

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 ERα(neg). 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(+)/CD49f(hi) 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-1(neg) 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(+)/CD49f(hi) MaSC population that may be responsible for the hormonal sensitivity of the developing mammary gland.

Original languageEnglish
Pages (from-to)417-431
Number of pages15
JournalStem Cell Reports
Volume8
Issue number2
Early online date26 Jan 2017
DOIs
Publication statusPublished - 14 Feb 2017

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  • Journal Article

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