Research Publications


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

Fu, NY; Rios, AC; Pal, B; Law, CW; Jamieson, P; Liu, R; Vaillant, F; Jackling, F; Liu, KH; Smyth, GK; Lindeman, GJ; Ritchie, ME; Visvader, JE
Nature Cell Biology
Journal Article
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.
Springer Nature
Stem Cells and Cancer; Molecular Medicine; Bioinformatics
Refer to article for additional funding acknowledgements
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Creation Date 2017-04-06 09:27:48 Last Modified 2018-03-20 01:27:19