Physical Poster + E-Poster Presentation 34th Lorne Cancer Conference 2022

Transcriptomic and chromatin profiling of mouse mammary epithelial cell identity (#116)

Melanie Stewart 1 , Genevieve Dall 2 , Emily Gruber 1 , Magnus Zethoven 1 , Bhupinder Pal 3 , Kara Britt 1
  1. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  2. Walter and Eliza Hall Institute, Melbourne, Victoria, Australia
  3. Olivia Newton-John Cancer Research Institute, Melbourne, Victoria, Australia

Breast cancer (BCa) currently affects one in seven women, and while mortality is decreasing, overall incidence is increasing. In particular, this increase is being driven by estrogen receptor positive (ER+) subtypes of BCa, likely due to changes in reproductive patterns including lack of childbearing, later menopause, and use of exogenous hormones. To elucidate how these factors impact BCa risk, we have assessed the molecular profile of each mammary epithelial cell lineage. This has been done using both transcript expression and the chromatin landscape in order to provide the most informative data on cell lineage and identity.  Using a modified version of the protocol established by Buenrostro et al., 2015, we have generated RNA- and ATAC-seq libraries from the same pellet of five FACS isolated mammary epithelial cell subsets. Analysis of these datasets has revealed novel markers of the cell types, including the poorly characterised common luminal progenitor cells, in addition to the ER- and ER+ luminal progenitors. Our assessment of chromatin architecture has revealed transcription factor motifs specific to each cell type, which together with the transcript profiles, defines the molecular control of each lineage. These datasets provide an unparalleled insight into mammary epithelial cell identity on the regulatory and transcript level, including importantly three distinct luminal progenitor populations thought to play a role in cancer risk.

  1. Buenrostro, J. D., Wu, B., Chang, H. Y., & Greenleaf, W. J. (2015). ATAC-seq: A Method for Assaying Chromatin Accessibility Genome-Wide. Current Protocols in Molecular Biology, 109, 21.29.1–21.29.9.