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

Nai Yang Fu, Anne C. Rios, Bhupinder Pal, Charity W. Law, Paul Jamieson, Ruijie Liu, François Vaillant, Felicity Jackling, Kevin He Liu, Gordon K. Smyth, Geoffrey J. Lindeman, Matthew E. Ritchie, Jane E. Visvader

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

86 Citaten (Scopus)

Samenvatting

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 + Tspan8 hi) resides within the proximal region throughout life, and has a transcriptome strikingly similar to that of claudin-low tumours. Lgr5 + 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.

Originele taal-2Engels
Pagina's (van-tot)164-176
Aantal pagina's13
TijdschriftNature Cell Biology
Volume19
Nummer van het tijdschrift3
DOI's
StatusGepubliceerd - 1 mrt. 2017
Extern gepubliceerdJa

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