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

doi:10.1016/j.stemcr.2016.12.022

Stem Cell Reports (Feb 2017)

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

Affiliations

Genevieve V. Dall: Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia
Jessica L. Vieusseux: Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia
Kenneth S. Korach: Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA
Yukitomo Arao: Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA
Sylvia C. Hewitt: Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA
Katherine J. Hamilton: Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA
Elaine Dzierzak: MRC Centre for Inflammation Research, University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK
Wah Chin Boon: The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia
Evan R. Simpson: Hudson Institute of Medical Research, Clayton, VIC 3168, Australia
Robert G. Ramsay: Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia
Torsten Stein: Institute of Cancer Sciences, College of MVLS, University of Glasgow, Glasgow G12 8QQ, UK
Joanne S. Morris: School of Veterinary Medicine, College of MVLS, University of Glasgow, Glasgow G61 1QH, UK
Robin L. Anderson: The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3010, Australia
Gail P. Risbridger: Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia
Kara L. Britt: Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia

DOI: https://doi.org/10.1016/j.stemcr.2016.12.022
Journal volume & issue: Vol. 8, no. 2
pp. 417 – 431

Abstract

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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.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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