Title: Human Stem Cell-Derived Neurons Repair Circuits and Restore Neural Function
Author: Man Xiong, Yezheng Tao, Qinqin Gao, Ban Feng, Wei Yan, Yingying Zhou, Thomas A. Kotsonis, Tingli Yuan, Zhiwen You, Ziyan Wu, Jiajie Xi, Alexander Haberman, Julia Graham, Jasper Block, Wenhao Zhou, Yuejun Chen, Su-Chun Zhang
Abstract: Although cell transplantation can rescue motor defects in Parkinson’s disease (PD)models, whether and how grafts functionally repair damaged neural circuitry in theadult brain is not known. We transplanted hESC-derived midbrain dopamine (mDA) orcortical glutamate neurons into the substantia nigra or striatum of a mouse PD model and found extensive graft integration with host circuitry.Axonal pathfinding toward the dorsal striatum was determined by the identity of thegrafted neurons, and anatomical presynaptic inputs were largely dependent on graftlocation, whereas inhibitory versus excitatory input was dictated by the identityof grafted neurons. hESC-derived mDA neurons display A9 characteristics and restorefunctionality of the reconstructed nigrostriatal circuit to mediate improvements inmotor function. These results indicate similarity in cell-type-specific pre- and post-synapticintegration between transplant-reconstructed circuit and endogenous neural networks,highlighting the capacity of hPSC-derived neuron subtypes for specific circuit repairand functional restoration in the adult brain.
Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：21.464