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 (), can aid in developing combination treatments with ARSI for advanced PCa patients.

中文翻译：

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综合单细胞分析定义了去势抵抗性前列腺管腔细胞的表观遗传基础


了解前列腺对去势和雄激素受体信号抑制剂 (ARSI) 的反应对于改善前列腺癌 (PCa) 患者的长期生存至关重要。在这里，我们对 229,794 个单细胞使用多组学方法来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背景，当与小鼠谱系追踪相结合时，证明去势抵抗管腔细胞与预先存在的尿道近端干/祖细胞不同。分子通路分析和治疗研究进一步表明 AP1 (JUN/FOS)、WNT/β-连环蛋白、FOXQ1、NF-κB 和 JAK/STAT 通路是与人类 PCa 相关的去势抵抗管腔群体的主要驱动因素。我们的数据集可通过交互式门户 () 进行探索，有助于为晚期 PCa 患者开发与 ARSI 的联合治疗。