The origin and dynamics of cellular heterogeneity vary across lineage subtypes of castrate resistant prostate cancer [scATAC-seq]

Cancer cells often adapt a stem-like state resulting in lineage plasticity and phenotypic heterogeneity. We assessed the dynamics of lineage determination and cellular subpopulation expansion in treatment-resistant adenocarcinoma, amphicrine, and small cell neuroendocrine castrate resistant prostate cancers. We used single-cell ATAC-seq to delineate the subpopulation structure of the heterogeneous organoids and define the lineage hierarchy, determine potential transcriptional regulators of amphicrine lineage-plasticity, and identify subpopulation-specific molecular targets for therapeutic intervention. ***Submitter declares that the raw data is being submitted to dbGaP (https://www.ncbi.nlm.nih.gov/gap) because of patient privacy concerns [accession ID phs001587.v2.p1]***