SoxC transcription factors are required for neuronal differentiation in adult hippocampal neurogenesis.
SoxC transcription factors are required for neuronal differentiation in adult hippocampal neurogenesis.
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DOI：
10.1523/jneurosci.4679-11.2012
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发表时间：
2012-02-29
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影响因子：
--
通讯作者：
Lie DC
中科院分区：
文献类型：
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作者：
Mu L;Berti L;Masserdotti G;Covic M;Michaelidis TM;Doberauer K;Merz K;Rehfeld F;Haslinger A;Wegner M;Sock E;Lefebvre V;Couillard-Despres S;Aigner L;Berninger B;Lie DC
神经干细胞（NSCs）在整个成年期产生新的海马齿状颗粒神经元。控制成体神经干细胞神经元分化的遗传程序知之甚少。在这里，我们表明，在成年小鼠海马，SoxC转录因子Sox 4和Sox 11的表达开始周围的成年神经干细胞的神经元承诺的时间，并保持在未成熟的神经元。Sox 4和Sox 11的过表达强烈促进成体神经干细胞的体外神经发生，而Sox 4/Sox 11的去除阻止成体神经干细胞的体外和体内神经发生。此外，我们证明了SoxC转录因子靶向成人神经干细胞神经元分化诱导的基因启动子。最后，我们表明，重新编程的星形胶质细胞成神经元依赖于SoxC因子的存在。这些数据确定了SoxC蛋白作为控制成体神经发生和体细胞神经元重编程中神经元分化的遗传网络的重要贡献者。
Neural stem cells (NSCs) generate new hippocampal dentate granule neurons throughout adulthood. The genetic programs controlling neuronal differentiation of adult NSCs are only poorly understood. Here we show that, in the adult mouse hippocampus, expression of the SoxC transcription factors Sox4 and Sox11 is initiated around the time of neuronal commitment of adult NSCs and is maintained in immature neurons. Overexpression of Sox4 and Sox11 strongly promotes in vitro neurogenesis from adult NSCs, whereas ablation of Sox4/Sox11 prevents in vitro and in vivo neurogenesis from adult NSCs. Moreover, we demonstrate that SoxC transcription factors target the promoters of genes that are induced on neuronal differentiation of adult NSCs. Finally, we show that reprogramming of astroglia into neurons is dependent on the presence of SoxC factors. These data identify SoxC proteins as essential contributors to the genetic network controlling neuronal differentiation in adult neurogenesis and neuronal reprogramming of somatic cells.