Using the Hierarchy to get Abreast of Cancer
Walter and Eliza Hall Institute
1g Royal Parade
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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. Recent single-cell RNA-seq studies have revealed rare breast epithelial subsets and heterogeneity within the different compartments. At a functional level, transplantation and lineage tracing strategies have proven to be essential for understanding the cell types that reside in breast tissue and their molecular regulators.
Professor Jane Visvader’s group has combined lineage tracing with a three-dimensional imaging strategy to explore the relative contributions of stem and progenitor cells to post-natal mammary gland development and tissue homeostasis. Cell lineage tracing studies also provide the current gold standard for identifying ‘cells of origin’ in cancer. Her group is utilising newly generated transgenic strains, harbouring lineage-specific gene regulatory regions, to direct the expression of specific mammary oncogenic lesions to distinct epithelial cell types. Interrogation of the molecular expression profiles of the diverse epithelial subsets in human breast tissue has also provided insight into potential ‘cells of origin’ of the different subtypes of cancer.
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