1. Altered Gene Expression of Thyroid Hormone Transporters and Deiodinases in iPS MeCP2-Knockout Cells-Derived Neurons.
- Author
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de Souza JS, Ferreira DR, Herai R, Carromeu C, Torres LB, Araujo BHS, Cugola F, Maciel RMB, Muotri AR, and Giannocco G
- Subjects
- Humans, Iodide Peroxidase metabolism, Karyotyping, Male, Membrane Transport Proteins metabolism, Metabolic Networks and Pathways, Models, Biological, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Neurons pathology, Rett Syndrome enzymology, Rett Syndrome genetics, Gene Expression Regulation, Induced Pluripotent Stem Cells metabolism, Iodide Peroxidase genetics, Membrane Transport Proteins genetics, Methyl-CpG-Binding Protein 2 deficiency, Neurons metabolism, Thyroid Hormones metabolism
- Abstract
MeCP2 is an X-linked gene; its mutation causes Rett Syndrome (RTT), a severe neurodevelopmental disability that affects mainly girls. Acting as a transcription factor, the MeCP2 protein is able to regulate several hormone-related genes, such as the thyroid hormones (TH), which are known to play an important role in the development of the central nervous system (CNS). Although only a few studies have associated RTT and TH, TH deficit can lead to neurological deregulation by triggering functional deficiencies during adulthood. Here, we used human-induced pluripotent stem cell (iPSC) to generate MeCP2-knockout neuronal progenitor cells and adult neurons. Using this cellular model, we then investigated the expression of genes associated with TH homeostasis, such as the TH transporters (LAT1, LAT2, MCT8, MCT10, and OATP4A1) and deiodinases (DIO1, 2, and 3). Then, we treated the neural cells with THs and analyzed the expression of several genes related to neurodevelopment and functional maintenance. Our results showed that several TH-related genes, such as deiodinases, are altered in RTT samples when compared to WT cells. Moreover, the treatment of the neural cells with THs increased the amount of MAP2 and synapsin-1 expression in RTT cells. Our work provided evidences that TH homeostasis is compromised in RTT-derived neural cells, which could be an important factor to contribute to the imbalance in the neurodevelopmental phenotype presented in this syndrome and can lead us to better understand other neurodevelopmental diseases.
- Published
- 2019
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