近日，美国加州大学教授Xianhua Piao及其课题组发现了小胶质细胞通过IGF1调控产前人脑GABA能神经发生。相关论文于2025年8月6日发表于国际顶尖学术期刊《自然》杂志上。

本研究揭示了小胶质细胞对人内侧神经节隆起（hMGE）中GABA能祖细胞和神经母细胞持续增殖的调控。该团队发现小胶质细胞优先分布在增殖区，并确定胰岛素样生长因子1 （IGF1）及其受体IGR1R是产前hMGE中小胶质细胞-祖细胞通讯的预测顶部配体-受体对。利用他们新开发的神经免疫类hMGE器官，模拟hMGE细胞结构和发育轨迹，课题组人员证明了小胶质细胞衍生的IGF1促进祖细胞增殖和GABA能神经元的产生。相反，IGF1中和抗体和IGF1敲除人胚胎干细胞诱导的小胶质细胞可消除诱导的小胶质细胞介导的祖细胞增殖。总之，这些发现揭示了小胶质细胞来源的IGF1在促进人脑神经祖细胞增殖和GABA能神经元发育中的作用，这是以前未被认识的。

据悉，GABA能神经元是神经回路的重要细胞组成部分。它们在人脑中的丰度和多样性显著增加，有助于扩大人类的认知能力。然而，GABA能神经元在人脑中的扩展产生的发育机制仍然是未知的。

附：英文原文

Title: Microglia regulate GABAergic neurogenesis in prenatal human brain through IGF1

Author: Yu, Diankun, Jain, Samhita, Wangzhou, Andi, Zhu, Beika, Shao, Wenyuan, Coley-ORourke, Elena J., De Florencio, Stacy, Kim, JaeYeon, Choi, Jennifer Ja-Yoon, Paredes, Mercedes F., Nowakowski, Tomasz J., Huang, Eric J., Piao, Xianhua

Issue&Volume: 2025-08-06

Abstract: GABAergic neurons are essential cellular components of neural circuits. Their abundance and diversity have increased significantly in the human brain, contributing to the expanded cognitive capacity of humans1. However, the developmental mechanism underlying the extended production of GABAergic neurons in the human brain remains elusive. Here we uncovered the microglial regulation of the sustained proliferation of GABAergic progenitors and neuroblasts in the human medial ganglionic eminence (hMGE). We showed that microglia are preferentially distributed in the proliferating zone and identified insulin-like growth factor 1 (IGF1) and its receptor IGR1R as the predicted top ligand–receptor pair underlying microglia–progenitor communication in the prenatal hMGE. Using our newly developed neuroimmune hMGE organoids, which mimic the hMGE cytoarchitecture and developmental trajectory, we demonstrated that microglia-derived IGF1 promotes progenitor proliferation and production of GABAergic neurons. Conversely, IGF1-neutralizing antibodies and IGF1 knockout human embryonic stem-cell-induced microglia abolish the induced microglia-mediated progenitor proliferation. Together, these findings revealed a previously unappreciated role of microglia-derived IGF1 in promoting the proliferation of neural progenitors and the development of GABAergic neurons in the human brain.

DOI: 10.1038/s41586-025-09362-8

Source: https://www.nature.com/articles/s41586-025-09362-8