Single-Cell Transcriptome Profiling of Thyroid Hormone Effectors in the Human Fetal Neocortex: Expression of SLCO1C1, DIO2, and THRB in Specific Cell Types
| Autor: | Juan Bernal, Diego Diez, Beatriz Morte |
|---|---|
| Přispěvatelé: | Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Instituto de Salud Carlos III, European Commission |
| Rok vydání: | 2021 |
| Předmět: |
endocrine system
endocrine system diseases Endocrinology Diabetes and Metabolism Type 2 deiodinas OATP1C1 DIO2 030209 endocrinology & metabolism Biology 03 medical and health sciences 0302 clinical medicine Endocrinology Fetus Interneurons Nuclear receptors Gene expression medicine Neocortex Triiodothyronine Effector Thyroid Cell biology medicine.anatomical_structure Nuclear receptor 030220 oncology & carcinogenesis MCT8 Hormone |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | © Diego Diez et al., 2021; Published by Mary Ann Liebert, Inc. [Background]: Thyroid hormones are crucial for brain development, acting through the thyroid hormone nuclear receptors (TR)α1 and β to control gene expression. Triiodothyronine (T3), the receptor-ligand, is transported into the brain from the blood by the monocarboxylate transporter 8 (MCT8). Another source of brain T3 is from the local deiodination of thyroxine (T4) by type 2 deiodinase (DIO2). While these mechanisms are very similar in mice and humans, important species-specific differences confound our understanding of disease using mouse models. To fill this knowledge gap on thyroid hormone action in the human fetal brain, we analyzed the expression of transporters, DIO2, and TRs, which we call thyroid hormone effectors, at single-cell resolution. [Methods]: We analyzed publicly available single-cell transcriptome data sets of isolated cerebral cortex neural cells from three different studies, with expression data from 393 to almost 40,000 cells. We generated Uniform Manifold Approximation and Projection scatterplots and cell clusters to identify differentially expressed genes between clusters, and correlated their gene signatures with the expression of thyroid effectors. [Results]: The radial glia, mainly the outer radial glia, and astrocytes coexpress SLCO1C1 and DIO2, indicating close cooperation between the T4 transporter OATP1C1 and DIO2 in local T3 formation. Strikingly, THRB was mainly present in two classes of interneurons: a majority expressing CALB2/calretinin, from the caudal ganglionic eminence, and in somatostatin-expressing interneurons from the medial ganglionic eminence. By contrast, many cell types express SLC16A2 and THRA. [Conclusions]:SLCO1C1 and DIO2 coexpression in the outer radial glia, the universal stem cell of the cerebral cortex, highlights the likely importance of brain-generated T3 in neurogenesis. The unique expression of THRB in discrete subsets of interneurons is a novel finding whose pathophysiological meaning deserves further investigation. This study was supported by grant #SAF2017-86342-R (Programa Estatal de Investigacion, Desarrollo e Innovacio´n Orientada a los Retos de la Sociedad), and the Center for Biomedical Research on Rare Diseases, Instituto de Salud Carlos III. The cost of this publication has been paid in part by FEDER funds. |
| Databáze: | OpenAIRE |
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