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Nat Cell Biol. 2017 Mar;19(3):164-176. doi: 10.1038/ncb3471. Epub 2017 Feb 13.

Identification of quiescent and spatially restricted mammary stem cells that are hormone responsive.

Author information

1
ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
2
Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
3
Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
4
Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
5
School of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria 3010, Australia.
6
Parkville Familial Cancer Centre, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Parkville, Victoria 3050, Australia.
7
Department of Medicine, The University of Melbourne, Parkville, Victoria 3010, Australia.

Abstract

Despite accumulating evidence for a mammary differentiation hierarchy, the basal compartment comprising stem cells remains poorly characterized. Through gene expression profiling of Lgr5+ basal epithelial cells, we identify a new marker, Tetraspanin8 (Tspan8). Fractionation based on Tspan8 and Lgr5 expression uncovered three distinct mammary stem cell (MaSC) subsets in the adult mammary gland. These exist in a largely quiescent state but differ in their reconstituting ability, spatial localization, and their molecular and epigenetic signatures. Interestingly, the deeply quiescent MaSC subset (Lgr5+Tspan8hi) resides within the proximal region throughout life, and has a transcriptome strikingly similar to that of claudin-low tumours. Lgr5+Tspan8hi cells appear to originate from the embryonic mammary primordia before switching to a quiescent state postnatally but can be activated by ovarian hormones. Our findings reveal an unexpected degree of complexity within the adult MaSC compartment and identify a dormant subset poised for activation in response to physiological stimuli.

PMID:
28192422
DOI:
10.1038/ncb3471
[Indexed for MEDLINE]

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