Purification and unique properties of mammary epithelial stem cells

John Stingl, Peter Eirew, Ian Ricketson, Mark Shackleton, François Vaillant, David Choi, Haiyan I. Li and Connie J. Eaves ()
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John Stingl: British Columbia Cancer Agency
Peter Eirew: British Columbia Cancer Agency
Ian Ricketson: British Columbia Cancer Agency
Mark Shackleton: WEHI Biotechnology Centre
François Vaillant: WEHI Biotechnology Centre
David Choi: British Columbia Cancer Agency
Haiyan I. Li: British Columbia Cancer Agency
Connie J. Eaves: British Columbia Cancer Agency

Nature, 2006, vol. 439, issue 7079, 993-997

Abstract: Abstract Elucidation of the cellular and molecular mechanisms that maintain mammary epithelial tissue integrity is of broad interest and paramount to the design of more effective treatments for breast cancer1. Evidence from both in vitro and in vivo experiments suggests that mammary cell differentiation is a hierarchical process originating in an uncommitted stem cell with self-renewal potential2,3,4. However, analysis of the properties and regulation of mammary stem cells has been limited by a lack of methods for their prospective isolation. Here we report the use of multi-parameter cell sorting and limiting dilution transplant analysis to demonstrate the purification of a rare subset of adult mouse mammary cells that are able individually to regenerate an entire mammary gland within 6 weeks in vivo while simultaneously executing up to ten symmetrical self-renewal divisions. These mammary stem cells are phenotypically distinct from and give rise to mammary epithelial progenitor cells that produce adherent colonies in vitro. The mammary stem cells are also a rapidly cycling population in the normal adult and have molecular features indicative of a basal position in the mammary epithelium.

Date: 2006
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DOI: 10.1038/nature04496

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