Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Viña del Mar, Chile.
Center for Aging and Regeneration, Faculty of Biological Sciences, P. Universidad Católica de Chile, Santiago, Chile.
Dev Dyn. 2023 Feb;252(2):294-304. doi: 10.1002/dvdy.535. Epub 2022 Sep 19.
The thyroid hormones-thyroxine (T4) and 3,5,3'triiodothyronine (T3)-regulate the development of the central nervous system (CNS) in vertebrates by acting in different cell types. Although several T3 target genes have been identified in the brain, the changes in the transcriptome in response to T3 specifically in neural stem and progenitor cells (NSPCs) during the early steps of NSPCs activation and neurogenesis have not been studied in vivo. Here, we characterized the transcriptome of FACS-sorted NSPCs in response to T3 during Xenopus laevis metamorphosis.
We identified 1252 upregulated and 726 downregulated genes after 16 hours of T3 exposure. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that T3-upregulated genes were significantly enriched in rRNA processing and maturation, protein folding, ribosome biogenesis, translation, mitochondrial function, and proteasome. These results suggest that NSPCs activation induced by T3 is characterized by an early proteome remodeling through the synthesis of the translation machinery and the degradation of proteins by the proteasome.
This work provides new insights into the dynamics of activation of NPSCs in vivo in response to T3 during a critical period of neurogenesis in the metamorphosis.
甲状腺激素-甲状腺素（T4）和 3,5,3'-三碘甲状腺原氨酸（T3）-通过在不同的细胞类型中作用来调节脊椎动物中枢神经系统（CNS）的发育。尽管已经在大脑中鉴定出了几个 T3 靶基因，但在神经干细胞和祖细胞（NSPC）的早期激活和神经发生过程中，T3 特异性地作用于 NSPC 时，其转录组的变化尚未在体内进行研究。在这里，我们在非洲爪蟾变态过程中，通过 FACS 分选 NSPC 来研究 T3 对其转录组的影响。
在 T3 暴露 16 小时后，我们鉴定出 1252 个上调和 726 个下调基因。基因本体论和京都基因与基因组百科全书（KEGG）分析表明，T3 上调的基因在 rRNA 加工和成熟、蛋白质折叠、核糖体生物发生、翻译、线粒体功能和蛋白酶体中显著富集。这些结果表明，T3 诱导的 NSPC 激活的特征是通过翻译机制的合成和蛋白酶体对蛋白质的降解，早期进行蛋白质组重塑。
这项工作为在神经发生的关键时期，T3 对体内 NSPC 激活的动态提供了新的见解。
