中国科学院分子细胞科学卓越创新中心高栋等研究人员合作发现，JAK/STAT信号通路在前列腺基底细胞命运决定过程中维持中间细胞群体。2024年11月13日，国际知名学术期刊《自然—遗传学》在线发表了这一成果。

研究人员鉴定了一种稀有的中间细胞群体，称为基底-B细胞。该群体表达腺泡标志物，具有增强的类器官形成能力，与较大的基底-A细胞群体不同。通过基因谱系追踪，研究人员发现基底-B细胞代表了前列腺稳态和雄激素介导再生过程中基底干细胞的一个过渡状态。

研究人员在基底-B细胞中发现了激活的JAK/STAT信号通路，且其抑制显著减少了基底-B标志物的表达。炎症增加了基底-B细胞向腺泡细胞的转分化，但JAK/STAT信号抑制显著减弱了这一效应。

Pten基因删除导致Nkx3.1表达的基底-B样细胞群体增多，并引发肿瘤发生。在人类中，h-基底-B细胞在良性前列腺增生中更为常见。

这项研究揭示了中间型基底-B 细胞的身份，并强调了JAK/STAT信号通路在前列腺细胞命运决定中的重要作用。

研究人员表示，前列腺的单能基底和腺泡干细胞维持着前列腺的稳态，而在前列腺炎症或癌症中，会出现一个中间细胞群体。然而，基底干细胞和中间细胞群体的身份仍不清楚。

附：英文原文

Title: JAK/STAT signaling maintains an intermediate cell population during prostate basal cell fate determination

Author: Guo, Wangxin, Zhang, Xiaoyu, Li, Lin, Shao, Pengfei, Liang, Chao, Zhang, Hongjiong, Liu, Kuo, Wang, Shuoming, Peng, Yunyi, Luo, Jun, Ju, Yi, De Marzo, Angelo M., Yu, Chen, Chen, Luonan, Zhou, Bin, Gao, Dong

Issue&Volume: 2024-11-13

Abstract: Unipotent basal and luminal stem cells maintain prostate homeostasis, with an intermediate cell population emerging during prostate inflammation or cancer. However, the identities of basal stem cell and intermediate cell population remain unclear. Here we identified a rare intermediate cell population expressing luminal markers (termed Basal-B) with enhanced organoid formation capacity, and a larger basal population (termed Basal-A). Genetic lineage tracing revealed Basal-B cells represented a transient basal stem cell state during prostate homeostasis and androgen-mediated regeneration. Activated JAK/STAT signaling was identified in Basal-B cells, and its inhibition significantly reduced Basal-B markers expression. Inflammation increased Basal-B-to-luminal cell transdifferentiation, but JAK/STAT inhibition notably attenuated this effect. Pten gene deletion increased Nkx3.1-expressing Basal-B-like cell population and led to neoplasia. In humans, h-Basal-B cells were more prevalent in benign prostate hyperplasia. This study reveals the identities of intermediate Basal-B cells and underscores the role of JAK/STAT signaling in prostate cell fate determination.

DOI: 10.1038/s41588-024-01979-1

Source: https://www.nature.com/articles/s41588-024-01979-1