de Souza Janaina S, Carromeu Cassiano, Torres Laila B, Araujo Bruno H S, Cugola Fernanda R, Maciel Rui M B, Muotri Alysson R, Giannocco Gisele
Department of Medicine, Laboratory of Endocrinology and Translational Medicine, Universidade Federal de São Paulo, UNIFESP/EPM, São Paulo, SP, Brazil.
Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular & Molecular Medicine, Stem Cell Program, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Hum Mol Genet. 2017 Jan 15;26(2):270-281. doi: 10.1093/hmg/ddw384.
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder in which the MECP2 (methyl CpG-binding protein 2) gene is mutated. Recent studies showed that RTT-derived neurons have many cellular deficits when compared to control, such as: less synapses, lower dendritic arborization and reduced spine density. Interestingly, treatment of RTT-derived neurons with Insulin-like Growth Factor 1 (IGF1) could rescue some of these cellular phenotypes. Given the critical role of IGF1 during neurodevelopment, the present study used human induced pluripotent stem cells (iPSCs) from RTT and control individuals to investigate the gene expression profile of IGF1 and IGF1R on different developmental stages of differentiation. We found that the thyroid hormone receptor (TRalpha 3) has a differential expression profile. Thyroid hormone is critical for normal brain development. Our results showed that there is a possible link between IGF1/IGF1R and the TRalpha 3 and that over expression of IGF1R in RTT cells may be the cause of neurites improvement in neural RTT-derived neurons.
瑞特综合征（RTT）是一种X连锁神经发育障碍疾病，其中MECP2（甲基CpG结合蛋白2）基因发生突变。最近的研究表明，与对照组相比，源自RTT的神经元存在许多细胞缺陷，例如：突触较少、树突分支较少以及棘突密度降低。有趣的是，用胰岛素样生长因子1（IGF1）处理源自RTT的神经元可以挽救其中一些细胞表型。鉴于IGF1在神经发育过程中的关键作用，本研究使用来自RTT患者和对照个体的人诱导多能干细胞（iPSC）来研究IGF1和IGF1R在不同分化发育阶段的基因表达谱。我们发现甲状腺激素受体（TRalpha 3）具有差异表达谱。甲状腺激素对正常脑发育至关重要。我们的结果表明，IGF1/IGF1R与TRalpha 3之间可能存在联系，并且RTT细胞中IGF1R的过表达可能是神经RTT衍生神经元中神经突改善的原因。
