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, Francois Vaillant, Felicity Jackling, Kevin He Liu, Gordon K Smyth, Geoffrey J Lindeman, Matthew E Ritchie, Jane E Visvader
NATURE CELL BIOLOGY | NATURE PUBLISHING GROUP | Published : 2017
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 strikingl..View full abstract
Awarded by Australian National Health and Medical Research Council (NHMRC)
Awarded by NHMRC Fellowship
We are grateful to the Animal, FACS, Monoclonal Antibody (Bundoora), Imaging and Histology facilities at WEHI and to M. Milevskiy for discussions. This work was supported by the Australian National Health and Medical Research Council (NHMRC) grants no. 1016701, no. 1024852, no. 1054618, no. 1059622, no. 1085191, no. 1086727, no. 1100807; NHMRC IRIISS; the Victorian State Government through Victorian Cancer Agency (VCA) funding and Operational Infrastructure Support; and the Australian Cancer Research Foundation. N.Y.F. and A.C.R. were supported by a National Breast Cancer Foundation (NBCF)/Cure Cancer Australia Fellowship; B.P. by a NHMRC Fellowship no. 1016571 and a VCA Fellowship; G.K.S., G.J.L., M.E.R. and J.E.V. by NHMRC Fellowships no. 1058892, no. 1078730, no. 1104924, no. 1102742.