title: Notch2 genetic fate mapping reveals two previously unrecognized mammary epithelial lineages.
abstract: Notch signalling is implicated in stem and progenitor cell fate control in numerous organs. Using conditional in vivo genetic labelling we traced the fate of cells expressing the Notch2 receptor paralogue and uncovered the existence of two previously unrecognized mammary epithelial cell lineages that we term S (Small) and L (Large). S cells appear in a bead-on-a-string formation and are embedded between the luminal and basal/myoepithelial layers in a unique reiterative pattern, whereas single or paired L cells appear among ductal and alveolar cells. Long-term lineage tracing and functional studies indicate that S and L cells regulate ipsi- and contralateral spatial placement of tertiary branches and formation of alveolar clusters. Our findings revise present models of mammary epithelial cell hierarchy, reveal a hitherto undescribed mechanism regulating branching morphogenesis and may have important implications for identification of the cell-of-origin of distinct breast cancer subtypes.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Sanja
authors.initials: S
authors.lastname: Šale
authors.forename: Daniel
authors.initials: D
authors.lastname: Lafkas
authors.forename: Spyros
authors.initials: S
authors.lastname: Artavanis-Tsakonas
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D051927:CD24 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D048429:Cell Size; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D007774:Lactation / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011247:Pregnancy; D051883:Receptor, Notch2 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013194:Staining and Labeling / Q000379:methods*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000737:chemistry; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D018396:Mucin-1; C497765:Notch2 protein, mouse; D051883:Receptor, Notch2; C577056:muc1 protein, mouse; D013629:Tamoxifen; C016601:afimoxifene; D001616:beta-Galactosidase