SCA-1 labels a subset of estrogen-responsive bipotential repopulating cells within the CD24+ CD49fhi 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 journalArticleResearchpeer-review

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. Mouse mammary stem cells are thought to be estrogen-receptor negative and receive hormonal influence via estrogen-receptor-positive luminal neighbors. In this article, Britt and colleagues describe a population within the mammary stem cell-enriched compartment that is estrogen-receptor positive and directly responsive to estrogens. This has implications for understanding how aberrant hormone exposure affects breast cancer risk.

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

Keywords

  • Estrogen
  • Mammary stem cells
  • Sca-1

Cite this

Dall, Genevieve V. ; Vieusseux, Jessica L. ; Korach, Kenneth S. ; Arao, Yukitomo ; Hewitt, Sylvia C. ; Hamilton, Katherine J. ; Dzierzak, Elaine ; Boon, Wah Chin ; Simpson, Evan R. ; Ramsay, Robert G. ; Stein, Torsten ; Morris, Joanne S. ; Anderson, Robin L. ; Risbridger, Gail P. ; Britt, Kara L. / SCA-1 labels a subset of estrogen-responsive bipotential repopulating cells within the CD24+ CD49fhi mammary stem cell-enriched compartment. In: Stem Cell Reports. 2017 ; Vol. 8, No. 2. pp. 417-431.
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title = "SCA-1 labels a subset of estrogen-responsive bipotential repopulating cells within the CD24+ CD49fhi mammary stem cell-enriched compartment",
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. Mouse mammary stem cells are thought to be estrogen-receptor negative and receive hormonal influence via estrogen-receptor-positive luminal neighbors. In this article, Britt and colleagues describe a population within the mammary stem cell-enriched compartment that is estrogen-receptor positive and directly responsive to estrogens. This has implications for understanding how aberrant hormone exposure affects breast cancer risk.",
keywords = "Estrogen, Mammary stem cells, Sca-1",
author = "Dall, {Genevieve V.} and Vieusseux, {Jessica L.} and Korach, {Kenneth S.} and Yukitomo Arao and Hewitt, {Sylvia C.} and Hamilton, {Katherine J.} and Elaine Dzierzak and Boon, {Wah Chin} and Simpson, {Evan R.} and Ramsay, {Robert G.} and Torsten Stein and Morris, {Joanne S.} and Anderson, {Robin L.} and Risbridger, {Gail P.} and Britt, {Kara L.}",
year = "2017",
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Dall, GV, Vieusseux, JL, Korach, KS, Arao, Y, Hewitt, SC, Hamilton, KJ, Dzierzak, E, Boon, WC, Simpson, ER, Ramsay, RG, Stein, T, Morris, JS, Anderson, RL, Risbridger, GP & Britt, KL 2017, 'SCA-1 labels a subset of estrogen-responsive bipotential repopulating cells within the CD24+ CD49fhi mammary stem cell-enriched compartment' Stem Cell Reports, vol. 8, no. 2, pp. 417-431. https://doi.org/10.1016/j.stemcr.2016.12.022

SCA-1 labels a subset of estrogen-responsive bipotential repopulating cells within the CD24+ CD49fhi mammary stem cell-enriched compartment. / Dall, Genevieve V.; Vieusseux, Jessica L.; Korach, Kenneth S.; Arao, Yukitomo; Hewitt, Sylvia C.; Hamilton, Katherine J.; Dzierzak, Elaine; Boon, Wah Chin; Simpson, Evan R.; Ramsay, Robert G.; Stein, Torsten; Morris, Joanne S.; Anderson, Robin L.; Risbridger, Gail P.; Britt, Kara L.

In: Stem Cell Reports, Vol. 8, No. 2, 14.02.2017, p. 417-431.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - SCA-1 labels a subset of estrogen-responsive bipotential repopulating cells within the CD24+ CD49fhi mammary stem cell-enriched compartment

AU - Dall, Genevieve V.

AU - Vieusseux, Jessica L.

AU - Korach, Kenneth S.

AU - Arao, Yukitomo

AU - Hewitt, Sylvia C.

AU - Hamilton, Katherine J.

AU - Dzierzak, Elaine

AU - Boon, Wah Chin

AU - Simpson, Evan R.

AU - Ramsay, Robert G.

AU - Stein, Torsten

AU - Morris, Joanne S.

AU - Anderson, Robin L.

AU - Risbridger, Gail P.

AU - Britt, Kara L.

PY - 2017/2/14

Y1 - 2017/2/14

N2 - 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. Mouse mammary stem cells are thought to be estrogen-receptor negative and receive hormonal influence via estrogen-receptor-positive luminal neighbors. In this article, Britt and colleagues describe a population within the mammary stem cell-enriched compartment that is estrogen-receptor positive and directly responsive to estrogens. This has implications for understanding how aberrant hormone exposure affects breast cancer risk.

AB - 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. Mouse mammary stem cells are thought to be estrogen-receptor negative and receive hormonal influence via estrogen-receptor-positive luminal neighbors. In this article, Britt and colleagues describe a population within the mammary stem cell-enriched compartment that is estrogen-receptor positive and directly responsive to estrogens. This has implications for understanding how aberrant hormone exposure affects breast cancer risk.

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