Shackleton Mark, Vaillant François, Simpson Kaylene J, Stingl John, Smyth Gordon K, Asselin-Labat Marie-Liesse, Wu Li, Lindeman Geoffrey J, Visvader Jane E
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Nature. 2006 Jan 5;439(7072):84-8. doi: 10.1038/nature04372.
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.
基于乳腺上皮片段移植可使小鼠乳腺再生这一证据，人们推测存在乳腺干细胞（MaSCs）。MaSCs在乳腺肿瘤发生中的潜在作用进一步激发了人们对其的兴趣。然而，由于缺乏明确的标志物，MaSCs的身份鉴定和纯化一直难以实现。我们基于细胞表面标志物分离出不同的小鼠乳腺细胞群体，并通过移植鉴定出一个高度富集MaSCs的亚群（Lin-CD29hiCD24+）。在此我们表明，一个带有LacZ转基因标记的单细胞能够在体内重建完整的乳腺。移植的细胞对管腔和肌上皮谱系均有贡献，并在妊娠期间产生功能性的小叶腺泡单位。这些细胞的自我更新能力通过克隆性生长的连续移植得以证明。为支持MaSCs在乳腺癌中可能发挥的作用，富含干细胞的亚群在MMTV-wnt-1小鼠的癌前乳腺组织中扩增，且含有更多数量的MaSCs。我们的数据证实，Lin-CD29hiCD24+群体中的单个细胞具有多能性和自我更新能力，这些特性将它们定义为MaSCs。
