| First Author | Kirk JS | Year | 2024 |
| Journal | Cell Stem Cell | Volume | 31 |
| Issue | 8 | Pages | 1203-1221.e7 |
| PubMed ID | 38878775 | Mgi Jnum | J:352542 |
| Mgi Id | MGI:7665152 | Doi | 10.1016/j.stem.2024.05.008 |
| Citation | Kirk JS, et al. (2024) Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells. Cell Stem Cell |
| abstractText | 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/beta-catenin, FOXQ1, NF-kappaB, 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. |
