1. The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050,
2. Bone Marrow Research Laboratories, Royal Melbourne Hospital, Parkville, Victoria 3050,
3. Department of Biochemistry and Molecular Biology, The University of Melbourne, Victoria 3010, Australia
4. Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada
5. Stem Cell Technologies Inc., 570 West 7th Avenue, Suite 400, Vancouver, British Columbia V5Z 1B3, Canada
6. †Present address: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA

Correspondence to: Geoffrey J. Lindeman^1,2Jane E. Visvader^1,2 Correspondence and requests for materials should be addressed to J.E.V. (Email: visvader@wehi.edu.au) or G.J.L. (Email: lindeman@wehi.edu.au).

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^{1, 2, 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^-CD29^hiCD24⁺) 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^-CD29^hiCD24⁺ population are multipotent and self-renewing, properties that define them as MaSCs.

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