Identification of quiescent and spatially restricted mammary stem cells that are hormone responsive.
Nai Yang FuAnne C RiosBhupinder PalCharity W LawPaul JamiesonRuijie LiuFrançois VaillantFelicity JacklingKevin He LiuAaron T L LunGeoffrey J LindemanMatthew E RitchieJane E VisvaderPublished in: Nature cell biology (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 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.
Keyphrases
- stem cells
- genome wide
- dna methylation
- gene expression
- poor prognosis
- neural stem cells
- single cell
- cell therapy
- induced apoptosis
- copy number
- rna seq
- young adults
- peripheral blood
- bone marrow
- drug delivery
- long non coding rna
- cell cycle arrest
- cell proliferation
- single molecule
- transcription factor
- genome wide analysis