Invited Speaker Presentation 29th Lorne Cancer Conference 2017

Unravelling a highly heterogeneous mammary stem cell compartment (#22)

Nai Yang Fu 1 2 , Anne C Rios 1 2 , Bhupinder Pal 1 , Charity Law 2 3 , Paul Jamieson 1 , Ruijie Liu 3 , François Vaillant 1 2 , Gordon K Smyth 4 5 , Matthew E Ritchie 3 5 , Geoffrey J Lindeman 1 6 7 , Jane Visvader 1 2
  1. ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia
  3. Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  4. Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  5. School of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, Australia
  6. Parkville Familial Cancer Centre, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Parkville, VIC, Australia
  7. Department of Medicine, The University of Melbourne, Parkville, VIC, Australia

Breast cancer is a highly heterogeneous disease at both the molecular and pathological levels. To understand this heterogeneity and ‘cells of origin’ of breast cancer, it is important to dissect the normal mammary epithelial hierarchy. Despite accumulating evidence for a mammary differentiation hierarchy, the basal compartment comprising stem cells remains poorly characterised. Through gene expression profiling of Lgr5+ versus Lgr5 basal epithelial cells, we identify a novel marker that led to the fractionation of three distinct mammary stem cell (MaSC) subsets in the adult gland. These exist in a largely quiescent state but differ in their repopulating ability, spatial localisation, and their molecular signatures. Interestingly, the dormant MaSC subset localises to the proximal region of the gland throughout life. These cells appear to originate from the embryonic mammary primordia before switching to a quiescent state post-natally but can be recruited into the cell cycle in response to hormones. Single cell gene expression analyses have also revealed unexpected complexity within the basal and luminal compartments. Moreover, analyses at different stages of development have provided insights into the earliest ‘lineage priming’ events.