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DOI 10.1038/s41586-026-10264-6

Медицинская библиотека · Nature · 2026

Androgen activity in the male embryonic hindbrain drives lethal PFA ependymoma.

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, Hébert Steven, Ng Karen, Mantione Krystin, Whetstone Heather, Maan Hassaan, Lakkis Hussein, Lee Juyeun, Ramakrishnan Sadeesh K, Pei Yanxin, Tang Yujie, Lin Frank Y, Aldave Guillermo, Gallo Marco, Friedlander Robert M, Notta Faiyaz, Donovan Laura K, Chintagumpala Murali, Wang Bo, Li Yun, De Carvalho Daniel D, Zhang Zhaolei, Mao Ying, Hua Wei, Eberhart Charles, Lucas Calixto-Hope G, Venneti Sriram, Sorensen Poul H, Delaidelli Alberto, Li Hao, Zhou Wenhao, Kirk Jason, Tang Dean G, Jiang Tao, Liu Hailong, Lathia Justin D, Suzuki Hiromichi, Rich Jeremy N, Stein Lincoln D, Jabado Nada, Ramaswamy Vijay, Lu Q Richard, Heimberger Amy B, Daniels Craig, Michealraj Kulandaimanuvel Antony, Kleinman Claudia L, Taylor Michael D

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Аннотация

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.

Для цитирования: 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, Hébert Steven, Ng Karen, Mantione Krystin, Whetstone Heather, Maan Hassaan, Lakkis Hussein, Lee Juyeun, Ramakrishnan Sadeesh K, Pei Yanxin, Tang Yujie, Lin Frank Y, Aldave Guillermo, Gallo Marco, Friedlander Robert M, Notta Faiyaz, Donovan Laura K, Chintagumpala Murali, Wang Bo, Li Yun, De Carvalho Daniel D, Zhang Zhaolei, Mao Ying, Hua Wei, Eberhart Charles, Lucas Calixto-Hope G, Venneti Sriram, Sorensen Poul H, Delaidelli Alberto, Li Hao, Zhou Wenhao, Kirk Jason, Tang Dean G, Jiang Tao, Liu Hailong, Lathia Justin D, Suzuki Hiromichi, Rich Jeremy N, Stein Lincoln D, Jabado Nada, Ramaswamy Vijay, Lu Q Richard, Heimberger Amy B, Daniels Craig, Michealraj Kulandaimanuvel Antony, Kleinman Claudia L, Taylor Michael D. Androgen activity in the male embryonic hindbrain drives lethal PFA ependymoma.. Nature. 2026. DOI: 10.1038/s41586-026-10264-6.

Предметные рубрики MeSH

AnimalsFemaleHumansMaleMiceAndrogen AntagonistsAndrogensBrain NeoplasmsCell DifferentiationCell ProliferationDisease Models, AnimalEpendymomaReceptors, AndrogenRhombencephalonSex CharacteristicsSignal Transduction
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