title: Lgr6 labels a rare population of mammary gland progenitor cells that are able to originate luminal mammary tumours.
abstract: The mammary gland is composed of a complex cellular hierarchy with unusual postnatal plasticity. The identities of stem/progenitor cell populations, as well as tumour-initiating cells that give rise to breast cancer, are incompletely understood. Here we show that Lgr6 marks rare populations of cells in both basal and luminal mammary gland compartments in mice. Lineage tracing analysis showed that Lgr6+cells are unipotent progenitors, which expand clonally during puberty but diminish in adulthood. In pregnancy or following stimulation with ovarian hormones, adult Lgr6+cells regained proliferative potency and their progeny formed alveoli over repeated pregnancies. Oncogenic mutations in Lgr6+cells resulted in expansion of luminal cells, culminating in mammary gland tumours. Conversely, depletion of Lgr6+cells in the MMTV-PyMT model of mammary tumorigenesis significantly impaired tumour growth. Thus, Lgr6 marks mammary gland progenitor cells that can initiate tumours, and cells of luminal breast tumours required for efficient tumour maintenance.
authors: Center for Innovative Medicine (CIMED), Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 83 Huddinge, Sweden.
authors: Leander
authors: L
authors: Blaas
authors: Adult Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors: Fabio
authors: F
authors: Pucci
authors: Adult Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors: Hendrik A
authors: HA
authors: Messal
authors: Center for Innovative Medicine (CIMED), Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 83 Huddinge, Sweden.
authors: Agneta B
authors: AB
authors: Andersson
authors: Adult Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors: E
authors: E
authors: Josue Ruiz
authors: Center for Innovative Medicine (CIMED), Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 83 Huddinge, Sweden.
authors: Marco
authors: M
authors: Gerling
authors: Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Novum, 141 83 Huddinge, Sweden.
authors: Iyadh
authors: I
authors: Douagi
authors: Experimental Histopathology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors: Bradley
authors: B
authors: Spencer-Dene
authors: Center for Innovative Medicine (CIMED), Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 83 Huddinge, Sweden.
authors: Alexandra
authors: A
authors: Musch
authors: Bioinformatics and Biostatistics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors: Richard
authors: R
authors: Mitter
authors: Advanced Sequencing Facility, The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, London NW7 1AA, UK.
authors: Leena
authors: L
authors: Bhaw
authors: Experimental Histopathology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors: Richard
authors: R
authors: Stone
authors: Center for Innovative Medicine (CIMED), Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 83 Huddinge, Sweden.
authors: Dorothee
authors: D
authors: Bornhorst
authors: Advanced Sequencing Facility, The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, London NW7 1AA, UK.
authors: Abdul K
authors: AK
authors: Sesay
authors: Division of Molecular Pathology and Cancer, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
authors: Jos
authors: J
authors: Jonkers
authors: Experimental Histopathology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors: Gordon
authors: G
authors: Stamp
authors: Tumour-Stroma Interactions in Cancer Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors: Ilaria
authors: I
authors: Malanchi
authors: Center for Innovative Medicine (CIMED), Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 83 Huddinge, Sweden.
authors: Rune
authors: R
authors: Toftgård
authors: Adult Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.|Faculty of Life Sciences &Medicine, King's College London, Guy's Campus, London SE1 1UL, UK.
authors: Axel
authors: A
authors: Behrens
mesh_terms: D000483:Alleles; D000818:Animals; D000831:Animals, Newborn; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D063646:Carcinogenesis / Q000473:pathology; D019070:Cell Lineage; D049109:Cell Proliferation; D002999:Clone Cells; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D006728:Hormones; C417544:LGR6 protein, human; C548022:Lgr6 protein, mouse; D043562:Receptors, G-Protein-Coupled