1. Terry Fox Laboratory, and
2. Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver V5Z 1L3, British Columbia, Canada
3. StemCell Technologies Inc., Vancouver V5Z 1B3, British Columbia, Canada
4. The Walter and Eliza Hall Institute of Medical Research, WEHI Biotechnology Centre, Parkville, Victoria 3050, Australia
5. Departments of Medical Genetics, Pathology and Laboratory Medicine, and Medicine, University of British Columbia, Vancouver V6T 1Z3, British Columbia, Canada

Correspondence to: Connie J. Eaves^1,5 Correspondence and request for materials should be directed to C.J.E. (Email: ceaves@bccrc.ca). The microarray data can be accessed online at StemBase (http://www.scgp.ca:8080/StemBase/) and at the Gene Expression Omnibus (series accession number GSE3711) at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE3711.

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 potential^{2, 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.

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