title: Identification of quiescent and spatially restricted mammary stem cells that are hormone responsive.
abstract: Despite accumulating evidence for a mammary differentiation hierarchy, the basal compartment comprising stem cells remains poorly characterized. Through gene expression profiling of Lgr5+basal epithelial cells, we identify a new marker, Tetraspanin8 (Tspan8). Fractionation based on Tspan8 and Lgr5 expression uncovered three distinct mammary stem cell (MaSC) subsets in the adult mammary gland. These exist in a largely quiescent state but differ in their reconstituting ability, spatial localization, and their molecular and epigenetic signatures. Interestingly, the deeply quiescent MaSC subset (Lgr5+Tspan8hi) resides within the proximal region throughout life, and has a transcriptome strikingly similar to that of claudin-low tumours. Lgr5+Tspan8hicells appear to originate from the embryonic mammary primordia before switching to a quiescent state postnatally but can be activated by ovarian hormones. Our findings reveal an unexpected degree of complexity within the adult MaSC compartment and identify a dormant subset poised for activation in response to physiological stimuli.
authors.affiliation: ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Nai Yang
authors.initials: NY
authors.lastname: Fu
authors.affiliation: ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Rios
authors.affiliation: ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Pal
authors.affiliation: Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.|Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
authors.forename: Charity W
authors.initials: CW
authors.lastname: Law
authors.affiliation: ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Jamieson
authors.affiliation: Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
authors.forename: Ruijie
authors.initials: R
authors.lastname: Liu
authors.affiliation: ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: François
authors.identifier: 0000-0003-3229-3760
authors.initials: F
authors.lastname: Vaillant
authors.affiliation: ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
authors.forename: Felicity
authors.initials: F
authors.lastname: Jackling
authors.affiliation: ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
authors.forename: Kevin He
authors.initials: KH
authors.lastname: Liu
authors.affiliation: Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|School of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Gordon K
authors.identifier: 0000-0001-9221-2892
authors.initials: GK
authors.lastname: Smyth
authors.affiliation: ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Parkville Familial Cancer Centre, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Parkville, Victoria 3050, Australia.|Department of Medicine, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Geoffrey J
authors.identifier: 0000-0001-9386-2416
authors.initials: GJ
authors.lastname: Lindeman
authors.affiliation: Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|School of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Ritchie
authors.affiliation: ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Visvader
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
chemical_list: D006728:Hormones