title: Generation of a functional mammary gland from a single stem cell.
abstract: The existence of mammary stem cells (MaSCs) has been postulated from evidence that the mammary gland can be regenerated by transplantation of epithelial fragments in mice. Interest in MaSCs has been further stimulated by their potential role in breast tumorigenesis. However, the identity and purification of MaSCs has proved elusive owing to the lack of defined markers. We isolated discrete populations of mouse mammary cells on the basis of cell-surface markers and identified a subpopulation (Lin-CD29hiCD24+) that is highly enriched for MaSCs by transplantation. Here we show that a single cell, marked with a LacZ transgene, can reconstitute a complete mammary gland in vivo. The transplanted cell contributed to both the luminal and myoepithelial lineages and generated functional lobuloalveolar units during pregnancy. The self-renewing capacity of these cells was demonstrated by serial transplantation of clonal outgrowths. In support of a potential role for MaSCs in breast cancer, the stem-cell-enriched subpopulation was expanded in premalignant mammary tissue from MMTV-wnt-1 mice and contained a higher number of MaSCs. Our data establish that single cells within the Lin-CD29hiCD24+ population are multipotent and self-renewing, properties that define them as MaSCs.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Shackleton
authors.forename: François
authors.initials: F
authors.lastname: Vaillant
authors.forename: Kaylene J
authors.initials: KJ
authors.lastname: Simpson
authors.forename: John
authors.initials: J
authors.lastname: Stingl
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Smyth
authors.forename: Marie-Liesse
authors.initials: ML
authors.lastname: Asselin-Labat
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Lindeman
authors.forename: Jane E
authors.initials: JE
authors.lastname: Visvader
mesh_terms: D000818:Animals; D051927:CD24 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D019012:Integrin beta1 / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D007763:Lac Operon / Q000235:genetics; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D033581:Stem Cell Transplantation
chemical_list: D051927:CD24 Antigen; D019012:Integrin beta1; D007633:Keratins