神经发生是从神经干细胞（NSC）生成新神经元的过程，在神经​​系统疾病中发挥着至关重要的作用。该过程涉及一系列步骤，包括 NSC 增殖、迁移和分化，这些步骤受到神经营养性 Trk 和成纤维细胞生长因子受体 (FGFR) 信号传导等多种途径的调节。尽管发现了许多能够调节神经发生各个阶段的化合物，但识别可以调节神经发生的多个细胞过程的药物仍然具有挑战性。在这里，通过筛选膳食功能性食品中的生物活性化合物，我们发现了一种黄酮类白杨素，它不仅能增强人类神经干细胞的增殖，还能促进神经元分化和神经突生长。进一步的机制研究表明，白杨素的作用通过抑制神经营养性原肌球蛋白受体激酶 B (TrkB) 受体而减弱。一致地，白杨素激活 TrkB 和下游 ERK1/2 和 AKT。有趣的是，我们发现 FGFR1 阻断也降低了白杨素的作用。此外，白杨素的长期治疗可提高脑源性神经营养因子以及 FGF1 和 FGF8 的水平。最后，发现白杨素通过增加类器官的扩张和折叠来促进人脑类器官的神经发生，这也是由 TrkB 和 FGFR1 信号传导介导的。总而言之，我们的研究表明，激活 TrkB 和 FGFR1 信号传导可能是神经系统疾病治疗干预的一个有前途的途径，而白杨素似乎是开发此类治疗的潜在候选者。© 2024 作者。北京干细胞与再生医学研究院和John Wiley联合出版的《细胞增殖》

Neurogenesis is the process of generating new neurons from neural stem cells (NSCs) and plays a crucial role in neurological diseases. The process involves a series of steps, including NSC proliferation, migration and differentiation, which are regulated by multiple pathways such as neurotrophic Trk and fibroblast growth factor receptors (FGFR) signalling. Despite the discovery of numerous compounds capable of modulating individual stages of neurogenesis, it remains challenging to identify an agent that can regulate multiple cellular processes of neurogenesis. Here, through screening of bioactive compounds in dietary functional foods, we identified a flavonoid chrysin that not only enhanced the human NSCs proliferation but also facilitated neuronal differentiation and neurite outgrowth. Further mechanistic study revealed the effect of chrysin was attenuated by inhibition of neurotrophic tropomyosin receptor kinase-B (TrkB) receptor. Consistently, chrysin activated TrkB and downstream ERK1/2 and AKT. Intriguingly, we found that the effect of chrysin was also reduced by FGFR1 blockade. Moreover, extended treatment of chrysin enhanced levels of brain-derived neurotrophic factor, as well as FGF1 and FGF8. Finally, chrysin was found to promote neurogenesis in human cerebral organoids by increasing the organoid expansion and folding, which was also mediated by TrkB and FGFR1 signalling. To conclude, our study indicates that activating both TrkB and FGFR1 signalling could be a promising avenue for therapeutic interventions in neurological diseases, and chrysin appears to be a potential candidate for the development of such treatments.© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.