Fragile X Syndrome Patient-Derived Neurons Developing in the Mouse Brain Show FMR1-Dependent Phenotypes

Fragile X syndrome (FXS) is the most commonly inherited form of developmental and intellectual disability. Here, we used a new approach, i.e. neurons derived from FXS patients and transplanted in the mouse brain, to study this disease. It provided new insights into the development of FXS neurons, by facilitating their development in a 3D context: we found that FXS neurons had an altered maturation process, and our data suggest that their synapses might be hyperactive. Comparative gene expression profiling analysis of RNA-seq data for FXS cells and their isogenic controls..

脆性X综合征（Fragile X syndrome, FXS）是最常见的遗传性发育与智力障碍类型。本研究采用全新研究策略，即将源自脆性X综合征患者的神经元移植至小鼠脑内，以此探究该疾病的发病机制。该策略通过在三维微环境中促进神经元发育，为脆性X综合征神经元的发育机制研究提供了全新视角：研究发现脆性X综合征神经元的成熟过程发生异常，且本研究数据表明其突触（synapses）可能处于过度激活状态。此外，本研究还针对脆性X综合征细胞及其同基因对照（isogenic controls）样本的RNA测序（RNA-seq）数据开展了比较基因表达谱分析。