Generation of a functional mammary gland from a single stem cell.
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.
Shackleton
Mark
M
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Vaillant
François
F
Simpson
Kaylene J
KJ
Stingl
John
J
Smyth
Gordon K
GK
Asselin-Labat
Marie-Liesse
ML
Wu
Li
L
Lindeman
Geoffrey J
GJ
Visvader
Jane E
JE
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
D051927:CD24 Antigen; D019012:Integrin beta1; D007633:Keratins