Tsc2 coordinates neuroprogenitor differentiation.
Tsc2 coordinates neuroprogenitor differentiation.
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Tsc2协调神经祖细胞分化。
DOI：
10.1016/j.isci.2023.108442
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发表时间：
2023-12-15
期刊：
影响因子：
5.8
通讯作者：
Feliciano, David M.
中科院分区：
文献类型：
--
作者：
Riley, Victoria A.;Shankar, Vijay;Holmberg, Jennie C.;Sokolov, Aidan M.;Neckles, Victoria N.;Williams, Kaitlyn;Lyman, Rachel;Mackay, Trudy F. C.;Feliciano, David M.
脑室-脑室下区(V-SVZ)的神经干细胞(NSCs)产生多种类型的细胞。在从茎向分化的过程中，mRNA转录的可获得性和翻译的解偶联发生。MTORC1K通路敏锐地控制着调节mRNA翻译的蛋白质。由于mTORC1调节子的体细胞突变扰乱了大脑的结构，因此在分化过程中抑制mTORC1被认为是大脑发育的关键。TSC1或TSC2基因的失活突变会导致结节性硬化症(TSC)。TSC患者在纹状体和脑室附近有生长。在这里，它证明了V-SVZ NSC TSC2失活导致纹状体错构瘤。去除TSC2改变了翻译因子、翻译体和翻译效率。体内TSC2缺失后的单核RNA测序显示了NSC激活状态的变化。错构瘤的未成熟表型保留的原因是不能将转录产物的可获得性与翻译延迟分化相结合。综上所述，TSC2是翻译抑制和分化所必需的。TSC2突变神经干细胞产生含有异位神经元的错构瘤TSC2突变神经干细胞mTORC1活性升高和翻译改变TSC2突变神经干细胞改变了过渡状态TSC2突变神经干细胞保留干细胞样表型分子生物学；基因调控的分子机制；神经科学；细胞生物学；干细胞研究；转录组学
Neural stem cells (NSCs) of the ventricular-subventricular zone (V-SVZ) generate numerous cell types. The uncoupling of mRNA transcript availability and translation occurs during the progression from stem to differentiated states. The mTORC1 kinase pathway acutely controls proteins that regulate mRNA translation. Inhibiting mTORC1 during differentiation is hypothesized to be critical for brain development since somatic mutations of mTORC1 regulators perturb brain architecture. Inactivating mutations of TSC1 or TSC2 genes cause tuberous sclerosis complex (TSC). TSC patients have growths near the striatum and ventricles. Here, it is demonstrated that V-SVZ NSC Tsc2 inactivation causes striatal hamartomas. Tsc2 removal altered translation factors, translatomes, and translational efficiency. Single nuclei RNA sequencing following in vivo loss of Tsc2 revealed changes in NSC activation states. The inability to decouple mRNA transcript availability and translation delayed differentiation leading to the retention of immature phenotypes in hamartomas. Taken together, Tsc2 is required for translational repression and differentiation. Tsc2 mutant neural stem cells generate hamartomas containing ectopic neurons Tsc2 mutant neural stem cells have elevated mTORC1 activity and altered translation Tsc2 mutant neural stem cells have altered transitional states Tsc2 mutant glia retain stem-like phenotypes Molecular biology; Molecular mechanism of gene regulation; Neuroscience; Cell biology; Stem cells research; Transcriptomics
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
7.7
作者：
Cebrian-Silla A;Nascimento MA;Redmond SA;Mansky B;Wu D;Obernier K;Romero Rodriguez R;Gonzalez-Granero S;García-Verdugo JM;Lim DA;Álvarez-Buylla A
通讯作者：
Álvarez-Buylla A
影响因子：
3.7
作者：
de Vries PJ;Belousova E;Benedik MP;Carter T;Cottin V;Curatolo P;Dahlin M;D'Amato L;d'Augères GB;Ferreira JC;Feucht M;Fladrowski C;Hertzberg C;Jozwiak S;Kingswood JC;Lawson JA;Macaya A;Marques R;Nabbout R;O'Callaghan F;Qin J;Sander V;Sauter M;Shah S;Takahashi Y;Touraine R;Youroukos S;Zonnenberg B;Jansen AC;TOSCA Consortium and TOSCA Investigators
通讯作者：
TOSCA Consortium and TOSCA Investigators
影响因子：
7.2
作者：
Bonaguidi, Michael A.;Stadel, Ryan P.;Song, Hongjun
通讯作者：
Song, Hongjun
影响因子：
4.8
作者：
Cox RL;Calderon de Anda F;Mangoubi T;Yoshii A
通讯作者：
Yoshii A