Molecular Mechanisms Regulating the Defects in Fragile X Syndrome Neurons Derived from Human Pluripotent Stem Cells

被引：66

作者：

Halevy, Tomer ^{[1
]}

Czech, Christian ^{[2
]}

Benvenisty, Nissim ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, Azrieli Ctr Stem Cells & Genet Res, IL-91904 Jerusalem, Israel

[2] Roche Innovat Ctr, CH-4070 Basel, Switzerland

来源：

STEM CELL REPORTS | 2015年 / 4卷 / 01期

基金：

以色列科学基金会;

关键词：

MENTAL-RETARDATION PROTEIN; RESTRICTIVE SILENCER FACTOR; GENOME-WIDE ANALYSIS; NEURAL STEM; IN-VIVO; PROGENITOR CELLS; GENE-EXPRESSION; TARGET GENES; FMR1; TRANSCRIPTION;

D O I：

10.1016/j.stemcr.2014.10.015

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Fragile X syndrome (FXS) is caused by the absence of the fragile X mental retardation protein (FMRP). We have previously generated FXS-induced pluripotent stem cells (iPSCs) from patients' fibroblasts. In this study, we aimed at unraveling the molecular phenotype of the disease. Our data revealed aberrant regulation of neural differentiation and axon guidance genes in FXS-derived neurons, which are regulated by the RE-1 silencing transcription factor (REST). Moreover, we found REST to be elevated in FXS-derived neurons. As FMRP is involved in the microRNA (miRNA) pathway, we employed miRNA-array analyses and uncovered several miRNAs dysregulated in FXS-derived neurons. We found hsa-mir-382 to be downregulated in FXS-derived neurons, and introduction of mimic-mir-382 into these neurons was sufficient to repress REST and upregulate its axon guidance target genes. Our data link FMRP and REST through the miRNA

引用

页码：37 / 46

页数：10

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