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Molecular hierarchy of mammary differentiation yields refined markers of mammary stem cells.


ABSTRACT: The partial purification of mouse mammary gland stem cells (MaSCs) using combinatorial cell surface markers (Lin(-)CD24(+)CD29(h)CD49f(h)) has improved our understanding of their role in normal development and breast tumorigenesis. Despite the significant improvement in MaSC enrichment, there is presently no methodology that adequately isolates pure MaSCs. Seeking new markers of MaSCs, we characterized the stem-like properties and expression signature of label-retaining cells from the mammary gland of mice expressing a controllable H2b-GFP transgene. In this system, the transgene expression can be repressed in a doxycycline-dependent fashion, allowing isolation of slowly dividing cells with retained nuclear GFP signal. Here, we show that H2b-GFP(h) cells reside within the predicted MaSC compartment and display greater mammary reconstitution unit frequency compared with H2b-GFP(neg) MaSCs. According to their transcriptome profile, H2b-GFP(h) MaSCs are enriched for pathways thought to play important roles in adult stem cells. We found Cd1d, a glycoprotein expressed on the surface of antigen-presenting cells, to be highly expressed by H2b-GFP(h) MaSCs, and isolation of Cd1d(+) MaSCs further improved the mammary reconstitution unit enrichment frequency to nearly a single-cell level. Additionally, we functionally characterized a set of MaSC-enriched genes, discovering factors controlling MaSC survival. Collectively, our data provide tools for isolating a more precisely defined population of MaSCs and point to potentially critical factors for MaSC maintenance.

SUBMITTER: dos Santos CO 

PROVIDER: S-EPMC3645536 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Molecular hierarchy of mammary differentiation yields refined markers of mammary stem cells.

dos Santos Camila O CO   Rebbeck Clare C   Rozhkova Elena E   Valentine Amy A   Samuels Abigail A   Kadiri Lolahon R LR   Osten Pavel P   Harris Elena Y EY   Uren Philip J PJ   Smith Andrew D AD   Hannon Gregory J GJ  

Proceedings of the National Academy of Sciences of the United States of America 20130411 18


The partial purification of mouse mammary gland stem cells (MaSCs) using combinatorial cell surface markers (Lin(-)CD24(+)CD29(h)CD49f(h)) has improved our understanding of their role in normal development and breast tumorigenesis. Despite the significant improvement in MaSC enrichment, there is presently no methodology that adequately isolates pure MaSCs. Seeking new markers of MaSCs, we characterized the stem-like properties and expression signature of label-retaining cells from the mammary gl  ...[more]

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