Dysregulation of neuron differentiation in an autistic savant with exceptional memory

• Type of Material: Article
• Authors: Jinjing Song, Shanghai Jiao Tong University; Xiujuan Yang, Shanghai Jiao Tong University; Ying Zhou, Emory University; Lei Chen, Shanghai Jiao Tong University; Xu Zhang, Shanghai Jiao Tong University; Zhuxi Liu, Shanghai Jiao Tong University; Weibo Niu, Shanghai Jiao Tong University; Nengpeng Zhan, Shanghai Jiao Tong University; Xuelian Fan, Shanghai Jiao Tong University; Abdul Aziz Khan, Shanghai Jiao Tong University; Yifang Kuang, Shanghai Jiao Tong University; Lulu Song, Shanghai Jiao Tong University; Guang He, Shanghai Jiao Tong University; Weidong Li, Shanghai Jiao Tong University
• Language: English
• Date: 2019-11-07
• Publisher: BMC (part of Springer Nature)
• Publication Version: Final Published Version
• Copyright Statement: © 2019 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13041-019-0507-7
• Title of Journal or Parent Work: Molecular Brain
• ISSN: 1756-6606
• Volume: 12
• Issue: 1
• Start Page: 91
• End Page: 91
• Grant/Funding Information: This work was supported by the National Natural Science Foundation of China (NSFC) 91632103; Program of Shanghai Subject Chief Scientist 17XD1401700; Shanghai Education Commission Research and Innovation Program 2019-01-07-00-02-E00037; “111” Program of Higher Education Discipline Innovation and “Eastern Scholar” (Shanghai Municipal Education Commission).
• Keywords: Human induced pluripotent stem cells; Neurosciences; SPEECH; PREVALENCE; PERSPECTIVE; Neurosciences & Neurology; FOXP2; GENERATION; GENES; Life Sciences & Biomedicine; PAX6; Autistic savant; TBR1; TALENTS; Neurons; PLURIPOTENT STEM-CELLS; SPECTRUM DISORDER; Science & Technology
• Research Categories: Psychology, Developmental; Biology, Neuroscience

Abstract

Autism spectrum disorder (ASD) is a heterogeneous group of complex neurodevelopmental disorders without a unique or definite underlying pathogenesis. Although savant syndrome is common in ASD, few models are available for studying the molecular and cellular mechanisms of this syndrome. In this study, we generated urinary induced pluripotent stem cells (UiPSCs) from a 13-year-old male autistic savant with exceptional memory. The UiPSC-derived neurons of the autistic savant exhibited upregulated expression levels of ASD genes/learning difficulty-related genes, namely PAX6, TBR1 and FOXP2, accompanied by hypertrophic neural somas, enlarged spines, reduced spine density, and an increased frequency of spontaneous excitatory postsynaptic currents. Although this study involved only a single patient and a single control because of the rarity of such cases, it provides the first autistic savant UiPSC model that elucidates the potential cellular mechanisms underlying the condition.