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Human stem cell-derived A10 dopaminergic neuronsspecifically integrate into mouse circuits andimprove depression-like behaviors by Wei Yan & Qinqin Gao & Yingying Zhou & Peibo Xu & Ziyan Wu & Tingli Yuan & Lianshun Xie & Zhiwen You & Xinyue Zhang & Ban Feng & Shanzheng Yang & Yuejun Chen & Man Xiong is a book available to read on EtoBox.

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Stem Cell, 32 (2025) 1457-1481. doi:10.1016/j.stem.2025.07.007SUMMARYA10 dopaminergic neurons located in the ventral tegmental area play central roles in reward-related and goaldirected behaviors and are proposed to be target cells for treatment of various psychiatric disorders,including depression. Here, we report an efficient differentiation method to generate A10-like midbrain dopaminergic (mDA) neurons from human pluripotent stem cells (hPSCs) and found that post-mitotic patterning byNotch inhibitor, glial cell line-derived neurotrophic factor (GDNF), and ascorbic acid (AA) induced A10 subtype specification. These hPSC-derived mDA neurons exhibited characteristics of the A10 subtype, includinggene expression profiles and electrophysiological properties. Moreover, grafted A10-like mDA neurons specifically project to their endogenous target brain regions and induce the anxiolytic phenotype in normal miceor antidepressant-like phenotypes in depression model mice. These results indicate that grafted A10-likemDA neurons can reconstruct specific circuits and functionally restore impaired circuits, highlighting thepromising application of hPSC-derived neuron subtypes in the treatm

Author

Wei Yan & Qinqin Gao & Yingying Zhou & Peibo Xu & Ziyan Wu & Tingli Yuan & Lianshun Xie & Zhiwen You & Xinyue Zhang & Ban Feng & Shanzheng Yang & Yuejun Chen & Man Xiong

Publisher

The Author(s)

Published

2025

Language

EN