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Hippocampal Neurogenesis Requires Cell-Autonomous Thyroid Hormone Signaling.
Stem Cell Reports ( IF 5.9 ) Pub Date : 2020-04-16 , DOI: 10.1016/j.stemcr.2020.03.014
Steffen Mayerl 1 , Heike Heuer 2 , Charles Ffrench-Constant 1
Affiliation  

Adult hippocampal neurogenesis is strongly dependent on thyroid hormone (TH). Whether TH signaling regulates this process in a cell-autonomous or non-autonomous manner remains unknown. To answer this question, we used global and conditional knockouts of the TH transporter monocarboxylate transporter 8 (MCT8), having first used FACS and immunohistochemistry to demonstrate that MCT8 is the only TH transporter expressed on neuroblasts and adult slice cultures to confirm a necessary role for MCT8 in neurogenesis. Both mice with a global deletion or an adult neural stem cell-specific deletion of MCT8 showed decreased expression of the cell-cycle inhibitor P27KIP1, reduced differentiation of neuroblasts, and impaired generation of new granule cell neurons, with global knockout mice also showing enhanced neuroblast proliferation. Together, our results reveal a cell-autonomous role for TH signaling in adult hippocampal neurogenesis alongside non-cell-autonomous effects on cell proliferation earlier in the lineage.



中文翻译:

海马神经发生需要细胞自主甲状腺激素信号转导。

成人海马神经发生强烈依赖于甲状腺激素(TH)。TH信号传导以细胞自主或非自主方式调节该过程仍然未知。为了回答这个问题,我们使用了TH转运蛋白单羧酸盐转运蛋白8(MCT8)的整体和条件敲除方法,首先使用FACS和免疫组织化学方法来证明MCT8是在成神经细胞和成年切片培养物中表达的唯一TH转运蛋白,以确认对于MCT8在神经发生中。整体缺失或成年​​神经干细胞特异性缺失MCT8的小鼠均显示出细胞周期抑制剂P27KIP1的表达降低,成神经细胞的分化减少,新颗粒细胞神经元的生成受损,而整体敲除小鼠也表现出增强的成神经细胞增殖。一起,

更新日期:2020-04-16
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