title: Mammary stem cells have myoepithelial cell properties.
abstract: Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt actin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using two independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage-tracing approach we follow the progeny of myoepithelial cells that express α-smooth muscle actin and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy.
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Prater
authors.affiliation: 1] Institut Curie, Centre de Recherche, Paris, F-75248, France [2] CNRS, UMR144, Paris, F-75248, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Petit
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
authors.forename: I
authors.initials: I
authors.lastname: Alasdair Russell
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
authors.forename: Rajshekhar R
authors.initials: RR
authors.lastname: Giraddi
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
authors.forename: Mona
authors.initials: M
authors.lastname: Shehata
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
authors.forename: Suraj
authors.initials: S
authors.lastname: Menon
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
authors.forename: Reiner
authors.initials: R
authors.lastname: Schulte
authors.affiliation: Reconstructive Sciences, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut 06030-3705, USA.
authors.forename: Ivo
authors.initials: I
authors.lastname: Kalajzic
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Rath
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Olson
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, (CNRS/INSERM/Université de Strasbourg/Collège de France), Illkirch Cedex 67404, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Metzger
authors.affiliation: 1] Institut Curie, Centre de Recherche, Paris, F-75248, France [2] CNRS, UMR144, Paris, F-75248, France.
authors.forename: Marisa M
authors.initials: MM
authors.lastname: Faraldo
authors.affiliation: 1] Institut Curie, Centre de Recherche, Paris, F-75248, France [2] CNRS, UMR144, Paris, F-75248, France.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Deugnier
authors.affiliation: 1] Institut Curie, Centre de Recherche, Paris, F-75248, France [2] CNRS, UMR144, Paris, F-75248, France.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Glukhova
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
authors.forename: John
authors.initials: J
authors.lastname: Stingl
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004149:Dioxoles / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D000199:Actins; D001549:Benzamides; D004149:Dioxoles; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D018125:Receptors, Transforming Growth Factor beta; D049452:Green Fluorescent Proteins