title: SCA-1 Labels a Subset of Estrogen-Responsive Bipotential Repopulating Cells within the CD24+CD49fhiMammary 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+/CD49fhiMaSCs. 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-1negcounterparts. 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+/CD49fhiMaSC population that may be responsible for the hormonal sensitivity of the developing mammary gland.
authors.affiliation: Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Genevieve V
authors.initials: GV
authors.lastname: Dall
authors.affiliation: Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Vieusseux
authors.affiliation: Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Korach
authors.affiliation: Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA.
authors.forename: Yukitomo
authors.initials: Y
authors.lastname: Arao
authors.affiliation: Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA.
authors.forename: Sylvia C
authors.initials: SC
authors.lastname: Hewitt
authors.affiliation: Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Hamilton
authors.affiliation: MRC Centre for Inflammation Research, University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Dzierzak
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Wah Chin
authors.initials: WC
authors.lastname: Boon
authors.affiliation: Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.
authors.forename: Evan R
authors.initials: ER
authors.lastname: Simpson
authors.affiliation: Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Ramsay
authors.affiliation: Institute of Cancer Sciences, College of MVLS, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Torsten
authors.initials: T
authors.lastname: Stein
authors.affiliation: School of Veterinary Medicine, College of MVLS, University of Glasgow, Glasgow G61 1QH, UK.
authors.forename: Joanne S
authors.initials: JS
authors.lastname: Morris
authors.affiliation: The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3010, Australia; La Trobe University, Bundoora, VIC 3083, Australia.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Anderson
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Gail P
authors.initials: GP
authors.lastname: Risbridger
authors.affiliation: Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: kara.britt@petermac.org.
authors.forename: Kara L
authors.initials: KL
authors.lastname: Britt
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D051927:CD24 Antigen / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D016130:Immunophenotyping; D039503:Integrin alpha6 / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000950:Antigens, Ly; D051927:CD24 Antigen; D047628:Estrogen Receptor alpha; D004967:Estrogens; D039503:Integrin alpha6; C074650:Ly6a protein, mouse; D008565:Membrane Proteins
keywords: Sca-1; estrogen; mammary stem cells