Identification of quiescent and spatially restricted mammary stem cells that are hormone responsive
- Author(s)
- 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;
- Details
- Publication Year 2017-03,Volume 19,Issue #3,Page 164-176
- Journal Title
- Nature Cell Biology
- Publication Type
- Journal Article
- 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.
- Publisher
- Springer Nature
- Research Division(s)
- Bioinformatics; Molecular Medicine; Stem Cells And Cancer
- PubMed ID
- 28192422
- Publisher's Version
- https://doi.org/10.1038/ncb3471
- NHMRC Grants
- NHMRC/1016701, NHMRC/1054618, NHMRC/1059622, NHMRC/1085191, NHMRC/1086727, NHMRC/1100807, NHMRC/1016571, NHMRC/1058892, NHMRC/1078730, NHMRC/1104924, NHMRC/1102742,
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- Refer to copyright notice on published article.
Creation Date: 2017-04-06 09:27:48
Last Modified: 2018-03-20 01:27:19