Generation of a functional mammary gland from a single stem cell

Mark Shackleton, Francois Vaillant, Kaylene J. Simpson, John Stingl, Gordon K. Smyth, Marie Liesse Asselin-Labat, Li Wu, Geoffrey J. Lindeman, Jane E. Visvader

Research output: Contribution to journalArticle

1443 Scopus citations

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 mice1-3. Interest in MaSCs has been further stimulated by their potential role in breast tumorigenesis4. 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.

Original languageEnglish (US)
Pages (from-to)84-88
Number of pages5
JournalNature
Volume439
Issue number7072
DOIs
StatePublished - Jan 5 2006

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    Shackleton, M., Vaillant, F., Simpson, K. J., Stingl, J., Smyth, G. K., Asselin-Labat, M. L., Wu, L., Lindeman, G. J., & Visvader, J. E. (2006). Generation of a functional mammary gland from a single stem cell. Nature, 439(7072), 84-88. https://doi.org/10.1038/nature04372