Generation of a functional mammary gland from a single stem cell
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. 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.
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Lineage tracing has identified long-lived stem cells in mammary epithelium and prostate.
“Lineage tracing experiments have also facilitated the identification of long-lived stem cells in the mammary epithelium36,37 and in glandular epithelia such as that found in the prostate38.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [37]
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- Authors
- Shackleton, M., Vaillant, F., Simpson, K. J., Stingl, J., Smyth, G. K., Asselin-Labat, M.-L., Wu, L., Lindeman, G. J., & Visvader, J. E.
- Affiliations
- The Royal Melbourne Hospital (AU)
- Harvard University (US)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Corresponding author
- Lindeman, Geoffrey J.
- Visvader, Jane E.
- ORCID
- Venue
- Nature
- Published
- 2006-01
- Volume
- 439
- Issue
- 7072
- Pages
- 84-88
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1979440527
- Cited by
- 2,005
- References
- 30
- Citations by year
- 2026: 23 · 2025: 35 · 2024: 38 · 2023: 70 · 2022: 65 · 2021: 72 · 2020: 86 · 2019: 81 · 2018: 67 · 2017: 88 · 2016: 95 · 2015: 124 · 2014: 132 · 2013: 136 · 2012: 160
- FWCI
- 74.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- mammary stem cells, mammary gland regeneration, single-cell transplantation, self-renewal, multipotency, beta1 integrin, CD24, breast tumorigenesis, mouse mammary gland
- MeSH terms
- Animals, Cell Differentiation, Cell Division, Epithelial Cells, Female, Keratins, Lac Operon, Mammary Glands, Animal, Mice, Transgenic, Regeneration, Genes, Reporter, Integrin beta1, Stem Cell Transplantation, Multipotent Stem Cells, Mice, CD24 Antigen
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