人类多能干细胞分化的A10样中脑多巴胺能神经元

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干细胞抗抑郁!中国科学院×复旦大学合作论文登上Cell Stem Cell封面
生物世界· 2025-09-06 09:00
Core Viewpoint - The research highlights the development of a method to efficiently differentiate human pluripotent stem cells (hPSCs) into A10-like midbrain dopaminergic neurons (A10 mDA), which can integrate into mouse brain circuits and alleviate depression-like behaviors [3][6][8]. Group 1: Research Methodology - The study established a protocol for differentiating hPSCs into A10 mDA neurons, demonstrating that these neurons can selectively integrate into host neural circuits and alleviate depression-like phenotypes [6][7]. - The differentiation process involved the use of Notch inhibitors, glial cell-derived neurotrophic factor (GDNF), and ascorbic acid (AA) to induce A10 subtype specification [7]. Group 2: Findings and Implications - The A10-like mDA neurons exhibited characteristics of the A10 subtype, including specific gene expression profiles and electrophysiological properties [7]. - Transplanted A10-like mDA neurons specifically projected to their endogenous target brain regions, inducing anxiolytic effects in normal mice and antidepressant-like effects in depression model mice [7][8]. - The findings suggest that therapies based on A10 mDA neurons hold potential for treating major depressive disorder and provide a theoretical basis for using hPSC-derived neuronal subtypes in treating a wide range of neuropsychiatric disorders [8].