ERG activates a stem-like proliferation-differentiation program in prostate epithelial cells with mixed basal-luminal identity [scATAC-seq]

Performed scATAC-seq in 3 timepoints of an autochthonous mouse model. A proliferative population is characterized by an ERG-specific chromatin state enriched for NFkB, AP-1, STAT and NFAT binding, with implications for TF cooperativity. ERG is enriched in a small stem-like population implicates the chromatin context of these cells as a critical variable for unmasking its oncogenic activity. A Rosa26-ERGLSL/LSL; Ptenflox/flox;Pb-Cre4 (EPC) mouse model, using single cell sequencing (scATAC-seq), at an early timepoint to capture changes associated with cancer initiation. At age 4 weeks, 3 months, and 6 months EPC mice have small foci of invasive cancer which subsequently progress to highly penetrant glandular invasion within 6 months