Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells.
Jason S KirkJie WangMark LongSpencer RosarioAmanda TraczYibing JiRahul KumarXiaozhuo LiuAnmbreen JamrozePrashant K SinghIgor PuzanovGurkamal ChattaQing ChengJiaoti HuangJeffrey L WranaJonathan LovellHan YuSong LiuMichael M ShenTao LiuDean G TangPublished in: Cell stem cell (2024)
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.
Keyphrases
- single cell
- prostate cancer
- rna seq
- induced apoptosis
- cell cycle arrest
- high throughput
- end stage renal disease
- signaling pathway
- gene expression
- radical prostatectomy
- benign prostatic hyperplasia
- chronic kidney disease
- stem cells
- cell proliferation
- endoplasmic reticulum stress
- oxidative stress
- newly diagnosed
- epithelial mesenchymal transition
- dna methylation
- pi k akt
- ejection fraction
- genome wide
- immune response
- dna damage
- machine learning
- single molecule