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Modeling Down Syndrome with Patient iPSCs Reveals Cellular and Migration Deficits of GABAergic Neurons

Year: 2018
Type: article
Abstract: The brain of Down syndrome (DS) patients exhibits fewer interneurons in the cerebral cortex, but its underlying mechanism remains unknown. By morphometric analysis of cortical interneurons generated from DS and euploid induced pluripotent stem cells (iPSCs), we found that DS GABA neurons are smaller and with fewer neuronal processes. The proportion of calretinin over calbindin GABA neurons is reduced, and the neuronal migration capacity is decreased. Such phenotypes were replicated following transplantation of the DS GABAergic progenitors into the mouse medial septum. Gene expression profiling revealed altered cell migratory pathways, and correction of the PAK1 pathway mitigated the cell migration deficit in vitro. These results suggest that impaired migration of DS GABAergic neurons may contribute to the reduced number of interneurons in the cerebral cortex and hippocampus in DS patients.
DOI: 10.1016/j.stemcr.2018.02.001
Authors: Hai-Qin Huo, Zhuang-Yin Qu, Fang Yuan, Lixiang Ma, Lin Yao, Min Xu, Yao Hu, Jing Ji, Anita Bhattacharyya, Su-Chun Zhang, Yan Liu
Institutions: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Shanghai Medical College of Fudan University, Fudan University, University of Wisconsin–Madison, Jiangsu Province Hospital, University of Wisconsin System
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $4,190
Funders: National Natural Science Foundation of China, Government of Jiangsu Province, National Institutes of Health, National Key Research and Development Program of China, National Institute of Mental Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1509114158, G1893859356, G2541829829, Analysis of human trisomy 21 interneuron progenitors, G4790023827, Early neurodevelopment origins of anxiety, Development and function of human astrocytes
OpenAlex ID: W2789849905
FWCI: 12.14
Cites: 47
Cited by: 124
Related to: 10