甲状腺激素转运体 MCT8 和 OATP1C1 缺失会影响成年小鼠侧脑室下区神经干细胞的命运。
Absence of Both Thyroid Hormone Transporters MCT8 and OATP1C1 Impairs Neural Stem Cell Fate in the Adult Mouse Subventricular Zone.
机构信息
UMR 7221 Phyma, CNRS/Muséum National d'Histoire Naturelle, 75005 Paris, France.
Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, 23562 Lübeck, Germany.
出版信息
Stem Cell Reports. 2021 Feb 9;16(2):337-353. doi: 10.1016/j.stemcr.2020.12.009. Epub 2021 Jan 14.
Adult neural stem cell (NSC) generation in vertebrate brains requires thyroid hormones (THs). How THs enter the NSC population is unknown, although TH availability determines proliferation and neuronal versus glial progenitor determination in murine subventricular zone (SVZ) NSCs. Mice display neurological signs of the severely disabling human disease, Allan-Herndon-Dudley syndrome, if they lack both MCT8 and OATP1C1 transporters, or MCT8 and deiodinase type 2. We analyzed the distribution of MCT8 and OATP1C1 in adult mouse SVZ. Both are strongly expressed in NSCs and at a lower level in neuronal cell precursors but not in oligodendrocyte progenitors. Next, we analyzed Mct8/Oatp1c1 double-knockout mice, where brain uptake of THs is strongly reduced. NSC proliferation and determination to neuronal fates were severely affected, but not SVZ-oligodendroglial progenitor generation. This work highlights how tight control of TH availability determines NSC function and glial-neuron cell-fate choice in adult brains.
成体神经干细胞（NSC）在脊椎动物脑中的产生需要甲状腺激素（THs）。尽管 TH 的可用性决定了鼠脑室下区（SVZ）NSC 的增殖以及神经元与神经胶质祖细胞的决定，但 TH 如何进入 NSC 群体尚不清楚。如果小鼠缺乏 MCT8 和 OATP1C1 转运体或 MCT8 和脱碘酶 2，则会表现出严重致残的人类疾病 Allan-Herndon-Dudley 综合征的神经学症状。我们分析了成年鼠 SVZ 中 MCT8 和 OATP1C1 的分布。两者在 NSCs 中强烈表达，在神经元前体细胞中表达水平较低，但在少突胶质前体细胞中不表达。接下来，我们分析了 Mct8/Oatp1c1 双敲除小鼠，其中 TH 的脑摄取明显减少。NSC 的增殖和向神经元命运的决定受到严重影响，但 SVZ-少突胶质祖细胞的产生不受影响。这项工作强调了 TH 可用性的严格控制如何决定成年大脑中 NSC 的功能和胶质-神经元细胞命运选择。
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