文章：

雄激素活性在雄性胚胎后脑驱动致死性PFA室管膜瘤

Androgen activity in the male embryonic hindbrain drives lethal PFA ependymoma

原文发布日期：2026-03-25

DOI: 10.1038/s41586-026-10264-6

类型: Article

开放获取: 是

英文摘要：

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.

摘要翻译： 

后颅窝A型（PFA）室管膜瘤是一种罕见的婴儿脑肿瘤，已知的体细胞突变较少，被认为由表观遗传机制驱动。该病在男性儿童中的发病率显著高于女性儿童，且预后更差。目前，这种性别差异背后的机制尚不明确。本研究表明，PFA室管膜瘤的细胞层级结构在男性个体中较女性个体分化程度更低。在正常发育的小鼠后脑中，雄性个体的胶质祖细胞分化程度低于同窝雌性对照。为进一步解析染色体与性腺贡献对雄性后脑发育的影响，我们使用了四核心基因型小鼠模型，结果显示雄激素信号（而非性染色体）延长了雄性小鼠的后脑分化过程。补充雄激素可促进PFA室管膜瘤的生长，但对其他脑肿瘤无此作用。相反，阻断雄激素信号则可降低PFA室管膜瘤的干细胞样潜能及其增殖能力。我们得出结论：在正常发育的后脑及PFA室管膜瘤中，雄激素信号均足以促进生长并延缓分化。抗雄激素疗法为治疗这种目前无法治愈的儿童肿瘤提供了潜在的临床新途径。

原文链接：

Androgen activity in the male embryonic hindbrain drives lethal PFA ependymoma