美国罗斯威尔公园综合癌症中心唐定国等合作取得一项新突破。他们利用综合单细胞分析确定了去势抵抗性前列腺腔细胞的表观遗传学基础。相关论文于2024年6月14日发表于国际顶尖学术期刊《细胞—干细胞》杂志上。

据悉，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。

研究组采用多组学方法对229,794个单细胞进行分析，以创建一个单细胞参考图谱，用于解释小鼠前列腺生物学和去势反应。他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，表明去势抵抗性腔细胞不同于先前存在的尿道近端干细胞/祖细胞。

分子通路分析和治疗研究进一步表明AP1 (JUN/FOS)、WNT/β-catenin、FOXQ1、NF-κB和JAK/STAT通路是与人类PCa相关的去势抵抗性腔群的主要驱动因素。他们的数据集可以通过交互式门户网站进行探索，可以帮助开发晚期PCa患者的ARSI联合治疗。

附：英文原文

Title: Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells

Author: Jason S. Kirk, Jie Wang, Mark Long, Spencer Rosario, Amanda Tracz, Yibing Ji, Rahul Kumar, Xiaozhuo Liu, Anmbreen Jamroze, Prashant K. Singh, Igor Puzanov, Gurkamal Chatta, Qing Cheng, Jiaoti Huang, Jeffrey L. Wrana, Jonathan Lovell, Han Yu, Song Liu, Michael M. Shen, Tao Liu, Dean G. Tang

Issue&Volume: 2024-06-14

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-cellreference atlas for interpreting mouse prostate biology and castration response. Ourreference atlas refines single-cell annotations and provides a chromatin context,which, when coupled with mouse lineage tracing, demonstrates that castration-resistantluminal cells are distinct from the pre-existent urethra-proximal stem/progenitorcells. 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-resistantluminal populations with relevance to human PCa. Our datasets, which can be exploredthrough an interactive portal (https://visportal.roswellpark.org/data/tang/), can aid in developing combination treatments with ARSI for advanced PCa patients.

DOI: 10.1016/j.stem.2024.05.008

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00185-1