title: Luminal progenitors restrict their lineage potential during mammary gland development.
abstract: The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.
authors: Department of Genetics and Developmental Biology, Institut Curie, Paris, France; Centre National de la Recherche Scientifique CNRS UMR3215, Paris, France; Institut National de la Santé et de la Recherche Médicale Inserm U934, Paris, France.
authors: Veronica
authors: V
authors: Rodilla
authors: Department of Genetics and Developmental Biology, Institut Curie, Paris, France; Centre National de la Recherche Scientifique CNRS UMR3215, Paris, France; Institut National de la Santé et de la Recherche Médicale Inserm U934, Paris, France.
authors: Alessandro
authors: A
authors: Dasti
authors: Department of Genetics and Developmental Biology, Institut Curie, Paris, France; Centre National de la Recherche Scientifique CNRS UMR3215, Paris, France; Institut National de la Santé et de la Recherche Médicale Inserm U934, Paris, France.
authors: Mathilde
authors: M
authors: Huyghe
authors: Department of Genetics and Developmental Biology, Institut Curie, Paris, France; Centre National de la Recherche Scientifique CNRS UMR3215, Paris, France; Institut National de la Santé et de la Recherche Médicale Inserm U934, Paris, France.
authors: Daniel
authors: D
authors: Lafkas
authors: Department of Translational Research, Institut Curie, Paris, France.
authors: Cécile
authors: C
authors: Laurent
authors: Department of Translational Research, Institut Curie, Paris, France; Department of Surgery, Institut Curie, Paris, France.
authors: Fabien
authors: F
authors: Reyal
authors: Department of Genetics and Developmental Biology, Institut Curie, Paris, France; Centre National de la Recherche Scientifique CNRS UMR3215, Paris, France; Institut National de la Santé et de la Recherche Médicale Inserm U934, Paris, France.
authors: Silvia
authors: S
authors: Fre
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics*; D058948:Cell Tracking; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055879:Gene Knock-In Techniques; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D038081:Organogenesis / Q000235:genetics*; D010641:Phenotype; D011247:Pregnancy; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; C045073:Cre recombinase; D019426:Integrases