Altered Gene Expression of Thyroid Hormone Transporters and Deiodinases in iPS MeCP2-Knockout Cells-Derived Neurons

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 i...

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Published in:	Molecular neurobiology Vol. 56; no. 12; pp. 8277 - 8295
Main Authors:	de Souza, Janaina Sena, Ferreira, Divino Romão, Herai, Roberto, Carromeu, Cassiano, Torres, Laila Brito, Araujo, Bruno Henrique Silva, Cugola, Fernanda, Maciel, Rui M. B., Muotri, Alysson Renato, Giannocco, Gisele
Format:	Journal Article
Language:	English
Published:	New York Springer US 01-12-2019 Springer Nature B.V
Subjects:	Biomedical and Life Sciences Biomedicine Cell Biology Central nervous system Deregulation Gene expression Gene Expression Regulation Homeostasis Humans Induced Pluripotent Stem Cells - metabolism Iodide Peroxidase - genetics Iodide Peroxidase - metabolism Karyotyping Male MeCP2 protein Membrane Transport Proteins - genetics Membrane Transport Proteins - metabolism Metabolic Networks and Pathways Methyl-CpG binding protein Methyl-CpG-Binding Protein 2 - deficiency Models, Biological Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Neural stem cells Neurobiology Neurodevelopmental disorders Neurology Neurons - metabolism Neurons - pathology Neurosciences Phenotypes Pluripotency Progenitor cells Rett syndrome Rett Syndrome - enzymology Rett Syndrome - genetics Synapsin Thyroid gland Thyroid hormones Thyroid Hormones - metabolism Deiodinase Thyroid hormones Gene expression Transporter gene mutation Rett syndrome MeCP2 gene mutation
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0893-7648 1559-1182
DOI:	10.1007/s12035-019-01645-2