PDF(Pubmed)
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.
摘要：
了解前列腺对去势和雄激素受体信号抑制剂（ARSI）的反应对于改善长期前列腺癌（PCa）患者的生存至关重要。这里,我们对229,794个单细胞使用了多组学方法,以创建小鼠单细胞参考图谱,用于解释小鼠前列腺生物学和去势反应.我们的参考图谱完善了单细胞注释，并提供了染色质上下文，which,当与小鼠谱系追踪相结合时，证明去势抗性腔细胞与先前存在的尿道近端干/祖细胞不同。分子途径分析和治疗研究进一步暗示AP1（JUN/FOS），WNT/β-连环蛋白，FOXQ1,NF-κB,和JAK/STAT途径是与人类PCa相关的去势抗性管腔群体的主要驱动因素。我们的数据集，可以通过交互式门户(https://visportal。roswellpark.org/data/tang/),可以帮助开发ARSI联合治疗晚期PCa患者。
