Mechanisms regulating stem cell plasticity during tumor initiation

Glandular epithelia, such as the mammary gland and the prostate, develop from multipotent stem cells (SCs), which are replaced in adult life by different types of lineage-restricted basal and luminal unipotent SCs. Upon oncogenic hits, the lineage restricted SCs can re-activate multipotent features reminiscent of the embryonic progenitors.  However, the molecular mechanisms regulating cell plasticity and oncogene-induced reprograming during mammary gland and prostate tumorigenesis are poorly understood. I will present new studies combining lineage tracing, clonal analysis, single cell RNA sequencing, chromatin profiling as well as in vitro and in vivo functional experiments investigate the cellular and molecular mechanisms regulating cell fate and plasticity during the early stage of mammary gland and prostate tumor initiation. Understanding how the mechanisms regulating SC fate and plasticity are corrupted during tumor initiation will have important implications for cancer prevention and therapy.