{Reference Type}: Journal Article
{Title}: Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells.
{Author}: Kirk JS;Wang J;Long M;Rosario S;Tracz A;Ji Y;Kumar R;Liu X;Jamroze A;Singh PK;Puzanov I;Chatta G;Cheng Q;Huang J;Wrana JL;Lovell J;Yu H;Liu S;Shen MM;Liu T;Tang DG;
{Journal}: Cell Stem Cell
{Volume}: 31
{Issue}: 8
{Year}: 2024 Aug 1
{Factor}: 25.269
{DOI}: 10.1016/j.stem.2024.05.008
{Abstract}: Understanding prostate response to castration and androgen receptor signaling inhibitors (ARSI) is critical to improving long-term prostate cancer (PCa) patient survival. Here, we use a multi-omics approach on 229,794 single cells to create a mouse single-cell reference atlas for interpreting mouse prostate biology and castration response. Our reference atlas refines single-cell annotations and provides a chromatin context, which, when coupled with mouse lineage tracing, demonstrates that castration-resistant luminal cells are distinct from the pre-existent urethra-proximal stem/progenitor cells. Molecular pathway analysis and therapeutic studies further implicate AP1 (JUN/FOS), WNT/β-catenin, FOXQ1, NF-κB, and JAK/STAT pathways as major drivers of castration-resistant luminal populations with relevance to human PCa. Our datasets, which can be explored through an interactive portal (https://visportal.roswellpark.org/data/tang/), can aid in developing combination treatments with ARSI for advanced PCa patients.