期刊
NATURE CELL BIOLOGY
卷 19, 期 3, 页码 164-176出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb3471
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资金
- Australian National Health and Medical Research Council (NHMRC) [1016701, 1024852, 1054618, 1059622, 1085191, 1086727, 1100807]
- NHMRC IRIISS
- Victorian State Government through Victorian Cancer Agency (VCA)
- Operational Infrastructure Support
- Australian Cancer Research Foundation
- National Breast Cancer Foundation (NBCF)/Cure Cancer Australia Fellowship
- NHMRC Fellowship [1016571, 1058892, 1078730, 1104924, 1102742]
- VCA Fellowship
- National Health and Medical Research Council of Australia [1059622, 1085191, 1086727, 1100807] Funding Source: NHMRC
Despite accumulating evidence for a mammary differentiation hierarchy, the basal compartment comprising stem cells remains poorly characterized. Through gene expression profiling of Lgr(5+) 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 (Lgr(5+)Tspan8(hi)) resides within the proximal region throughout life, and has a transcriptome strikingly similar to that of claudin-low tumours. Lgr(5+)Tspan8(hi) 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.
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