title: Enrichment for Repopulating Cells and Identification of Differentiation Markers in the Bovine Mammary Gland.
abstract: Elucidating cell hierarchy in the mammary gland is fundamental for understanding the mechanisms governing its normal development and malignant transformation. There is relatively little information on cell hierarchy in the bovine mammary gland, despite its agricultural potential and relevance to breast cancer research. Challenges in bovine-to-mouse xenotransplantation and difficulties obtaining bovine-compatible antibodies hinder the study of mammary stem-cell dynamics in this species. In-vitro indications of distinct bovine mammary epithelial cell populations, sorted according to CD24 and CD49f expression, have been provided. Here, we successfully transplanted these bovine populations into the cleared fat pads of immunocompromised mice, providing in-vivo evidence for the multipotency and self-renewal capabilities of cells that are at the top of the cell hierarchy (termed mammary repopulating units). Additional outgrowths from transplantation, composed exclusively of myoepithelial cells, were indicative of unipotent basal stem cells or committed progenitors. Sorting luminal cells according to E-cadherin revealed three distinct populations: luminal progenitors, and early- and late-differentiating cells. Finally, miR-200c expression was negatively correlated with differentiation levels in both the luminal and basal branches of the bovine mammary cell hierarchy. Together, these experiments provide further evidence for the presence of a regenerative entity in the bovine mammary gland and for the multistage differentiation process within the luminal lineage.
authors.affiliation: Institute of Animal Science, ARO, The Volcani Center, Bet-Dagan, Israel.|The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Gat
authors.initials: G
authors.lastname: Rauner
authors.affiliation: Institute of Animal Science, ARO, The Volcani Center, Bet-Dagan, Israel. itamar.barash@mail.huji.ac.il.
authors.forename: Itamar
authors.initials: I
authors.lastname: Barash
mesh_terms: D000273:Adipose Tissue; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D002454:Cell Differentiation; D002469:Cell Separation; D017690:Cell Transplantation; D002478:Cells, Cultured; D003433:Crosses, Genetic; D005260:Female; D005786:Gene Expression Regulation; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D000072356:Parenchymal Tissue / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D034622:RNA Interference; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D015415:Biomarkers; D015820:Cadherins; D035683:MicroRNAs
keywords: Bovine; E-cadherin; Mammary gland; Stem cells; Xenotransplantation; miR-200c