遗传背景和性别调节人类大脑微生理系统中的雄激素反应
bioRxiv : the preprint server for biology
|December 19, 2025
概括
像二测试 (DHT) 一样,雄激素信号传递通过改变神经器官中的细胞群和基因表达来显著影响人类大脑发育. 这些效应受到遗传背景的影响,可以改变神经发育途径.
科学领域:
- 神经科学是一个神经科学.
- 发育生物学 发展生物学
- 遗传学 是一个遗传学.
背景情况:
- 性类固醇对人类大脑发育至关重要.
- 雄激素的特定细胞和分子效应需要进一步研究.
- 人类神经器官模型为研究这些影响提供了一个平台.
研究的目的:
- 模拟二二 (DHT) 对来自诱导多能干细胞 (iPSC) 的人类神经器官的影响.
- 研究雄激素信号传递的转录,细胞和表观遗传后果.
- 探索遗传背景和性别如何影响发育中的大脑中的雄激素反应.
主要方法:
- 利用使用九条iPSC线的脑微生理系统 (bMPS) 模型.
- 管理的二测试 (DHT) 和分析的有机体反应.
- 采用大量的RNA测序,细胞类型表达特征,免疫组织化学和DNA甲基化分析.
- 使用同位素XX/XY线来区分性别染色体影响与DHT影响.
主要成果:
- DHT具有生物可用性,转移了雄激素受体 (AR),并激活了mTOR和代谢途径.
- 转录反应因供体背景而异,汇聚在线粒体能量,溶酶体功能和亡上.
- 在男性有机体中,DHT诱导了转向星系特征的转变,减少了神经元和寡细胞的特征.
- 雄激素信号改变了神经发育路径,具有自闭症谱系障碍 (ASD) 和状态缓解效应.
- DHT诱导了广泛的DNA甲基化变化,包括HOX基因和突触基因.
结论:
- 雄激素信号深深地塑造神经器官转录,细胞群和表观遗传学,以基因背景依赖的方式.
- DHT影响细胞类型组成和神经发育途径,对神经发育障碍有潜在的影响.
- 这项研究强调了体外模型对于理解大脑发育和疾病的个体间变异性的有用性.
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