近日，得克萨斯儿童医院Michael D. Taylor及其课题组的研究开发出了雄性胚胎后脑雄激素活性驱动致死性PFA室管膜瘤。该研究于2026年3月25日发表于国际一流学术期刊《自然》杂志上。

在这里，该团队发现PFA室管膜瘤的细胞等级在男性个体中比在女性个体中分化更少。在正常发育的母母后脑中，雄性胶质祖细胞分化程度低于匹配的雌性同胞对照。为了进一步分析染色体对雄性后脑的性腺贡献的影响，该研究团队对其核心基因型小鼠模型进行了主题化，该模型表明雄激素信号传导而不是性染色体延长了雄性小鼠后脑的分化。雄激素补充促进PFA室管膜瘤的生长，但对其他脑肿瘤没有促进作用。相反，雄激素阻断可减少PFA室管膜瘤的干样潜能和增殖。该课题组人员得出结论，雄激素信号在正常发育的后脑和PFA室管膜瘤中都足以促进生长和延迟分化。抗雄激素疗法代表了针对这种目前无法治疗的儿童癌症的潜在临床途径。

据了解，后窝A型室管膜瘤是一种罕见的婴儿脑瘤，很少有已知的体细胞突变，被认为是由表观遗传机制驱动的。PFA室管膜瘤在男性儿童中的发病率明显高于女性儿童，且预后较差。这些性别差异背后的机制目前尚不清楚。

附：英文原文

Title: Androgen activity in the male embryonic hindbrain drives lethal PFA ependymoma

Author: Zhang, Jiao, Ong, Winnie, Rasnitsyn, Alexandra, Gonzalez, Ricardo Daniel, Lopez Gutierrez, Rodrigo, Balin, Polina, Saadeldin, Amr, Wu, Xiaochong, Vladoiu, Maria C., Santa-Maria Lopez, Vicente, Gonzalez-Salinas, Fernando, Yadav, Navneesh, Mohanakrishnan, Dinesh, Boosi Narayana Rao, Kannan, Mooli, Raja Gopal Reddy, Najem, Hinda, Pacheco, Sebastian, Kharas, Kaitlin, Richman, Cory, Przelicki, David, Wang, Evan Y., Su, Haipeng, Curry, Rachel Naomi, Yang, Runze, Kameda-Smith, Michelle Masayo, Livingston, Bryn, Scott, David, Luo, Zaili, Xia, Mingyang, Abeysundara, Namal, Erickson, Anders W., Mankahla, Ncedile, Hu, Lucas ZhongMing, Pan, Chu, Suarez, Raul, Huang, Ning, Wu, Yihao, Wang, Hao, Douglas, Tajana, Pallota, Jonelle, Hbert, Steven, Ng, Karen, Mantione, Krystin, Whetstone, Heather, Maan, Hassaan, Lakkis, Hussein, Lee, Juyeun, Ramakrishnan, Sadeesh K., Pei, Yanxin, Tang, Yujie, Lin, Frank Y.

Issue&Volume: 2026-03-25

Abstract: Posterior fossa type A (PFA) ependymoma is an unusual infantile brain tumour with few known somatic mutations, thought to be driven by epigenetic mechanisms1. PFA ependymoma has a markedly higher incidence and worse prognosis in male children than in female children2. The mechanisms that underlie these sex differences are at present unknown. Here we show that the cellular hierarchy of PFA ependymoma is less differentiated in male individuals than it is in female individuals. In the normal developing mouse hindbrain, male gliogenic progenitors are less differentiated than matched female sibling controls. To further parse the effects of chromosomal versus gonadal contributions in the male hindbrain, we used the four-core genotype mouse model3, which showed that androgen signalling, rather than sex chromosomes, prolongs hindbrain differentiation in male mice. Androgen supplementation promotes the growth of PFA ependymoma, but not that of other brain tumours. Conversely, androgen blockade diminishes both the stem-like potential and the proliferation of PFA ependymoma. We conclude that androgen signalling in both the normal developing hindbrain and PFA ependymoma is sufficient to promote growth and delay differentiation. Anti-androgen therapies represent a potential clinical avenue to target this currently untreatable childhood cancer.

DOI: 10.1038/s41586-026-10264-6

Source: https://www.nature.com/articles/s41586-026-10264-6