PMID- 16397499 OWN - NLM STAT- MEDLINE DCOM- 20060124 LR - 20220812 IS - 1476-4687 (Electronic) IS - 0028-0836 (Linking) VI - 439 IP - 7072 DP - 2006 Jan 5 TI - Generation of a functional mammary gland from a single stem cell. PG - 84-8 AB - 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. FAU - Shackleton, Mark AU - Shackleton M AD - The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia. FAU - Vaillant, Francois AU - Vaillant F FAU - Simpson, Kaylene J AU - Simpson KJ FAU - Stingl, John AU - Stingl J FAU - Smyth, Gordon K AU - Smyth GK FAU - Asselin-Labat, Marie-Liesse AU - Asselin-Labat ML FAU - Wu, Li AU - Wu L FAU - Lindeman, Geoffrey J AU - Lindeman GJ FAU - Visvader, Jane E AU - Visvader JE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (CD24 Antigen) RN - 0 (Integrin beta1) RN - 68238-35-7 (Keratins) SB - IM MH - Animals MH - CD24 Antigen/metabolism MH - Cell Differentiation MH - Cell Division MH - Epithelial Cells/cytology/metabolism MH - Female MH - Genes, Reporter/genetics MH - Integrin beta1/metabolism MH - Keratins/metabolism MH - Lac Operon/genetics MH - Mammary Glands, Animal/*cytology/*physiology MH - Mice MH - Mice, Transgenic MH - Multipotent Stem Cells/*cytology/metabolism MH - Regeneration/*physiology MH - Stem Cell Transplantation EDAT- 2006/01/07 09:00 MHDA- 2006/01/25 09:00 CRDT- 2006/01/07 09:00 PHST- 2005/08/01 00:00 [received] PHST- 2005/10/13 00:00 [accepted] PHST- 2006/01/07 09:00 [pubmed] PHST- 2006/01/25 09:00 [medline] PHST- 2006/01/07 09:00 [entrez] AID - nature04372 [pii] AID - 10.1038/nature04372 [doi] PST - ppublish SO - Nature. 2006 Jan 5;439(7072):84-8. doi: 10.1038/nature04372.