title: Global Transcriptome Analysis of Primary Cerebrocortical Cells: Identification of Genes Regulated by Triiodothyronine in Specific Cell Types.
abstract: Thyroid hormones, thyroxine, and triiodothyronine (T3) are crucial for cerebral cortex development acting through regulation of gene expression. To define the transcriptional program under T3 regulation, we have performed RNA-Seq of T3-treated and untreated primary mouse cerebrocortical cells. The expression of 1145 genes or 7.7% of expressed genes was changed upon T3 addition, of which 371 responded to T3 in the presence of cycloheximide indicating direct transcriptional regulation. The results were compared with available transcriptomic datasets of defined cellular types. In this way, we could identify targets of T3 within genes enriched in astrocytes and neurons, in specific layers including the subplate, and in specific neurons such as prepronociceptin, cholecystokinin, or cortistatin neurons. The subplate and the prepronociceptin neurons appear as potentially major targets of T3 action. T3 upregulates mostly genes related to cell membrane events, such as G-protein signaling, neurotransmission, and ion transport and downregulates genes involved in nuclear events associated with the M phase of cell cycle, such as chromosome organization and segregation. Remarkably, the transcriptomic changes induced by T3 sustain the transition from fetal to adult patterns of gene expression. The results allow defining in molecular terms the elusive role of thyroid hormones on neocortical development.
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.|Center for Biomedical Research on Rare Diseases, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Gil-Ibañez
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: García-García
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.|Bioinformatics of Rare Diseases (BIER), CIBER de Enfermedades Raras (CIBERER), Valencia, Spain.|Functional Genomics Node, INB at CIPF, Valencia, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.|Center for Biomedical Research on Rare Diseases, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Bernal
authors.affiliation: Center for Biomedical Research on Rare Diseases, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Morte
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism; D059467:Transcriptome; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D010879:Piperazines; C000607849:RN-1665; D014284:Triiodothyronine
keywords: development; gene regulation; subplate; thyroid hormones; transcriptomics