Direct reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx2.
Direct reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx2.
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DOI：
10.1038/s41598-021-82931-9
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发表时间：
2021-02-11
影响因子：
4.6
通讯作者：
Nishiyama A
中科院分区：
文献类型：
--
作者：
Boshans LL;Soh H;Wood WM;Nolan TM;Mandoiu II;Yanagawa Y;Tzingounis AV;Nishiyama A
少突胶质细胞前体细胞（NG2胶质细胞）是哺乳动物中枢神经系统中均匀分布的增殖细胞，一生中产生髓鞘少突胶质细胞。新皮质中的OPCs亚群来自胚胎神经节隆起中的祖细胞，其也产生抑制性神经元。一些祖细胞的神经元命运在出生前就被锁定，因为它们定型为少突胶质细胞谱系，其特征在于少突胶质细胞转录因子Olig2的持续表达，Olig2抑制中间神经元转录因子Dlx 2。在这里，我们表明，在出生后的小鼠OPCs中，Dlx 2单独的错误表达导致它们在2天内通过下调Olig2和上调抑制性神经元转录物的网络而将其命运切换到GABA能神经元。两周后，一些OPC衍生的神经元产生一连串的动作电位，并形成GABA能突触蛋白簇。我们的研究表明，发育分子逻辑可以应用于促进OPCs的神经元重编程。
Oligodendrocyte precursor cells (NG2 glia) are uniformly distributed proliferative cells in the mammalian central nervous system and generate myelinating oligodendrocytes throughout life. A subpopulation of OPCs in the neocortex arises from progenitor cells in the embryonic ganglionic eminences that also produce inhibitory neurons. The neuronal fate of some progenitor cells is sealed before birth as they become committed to the oligodendrocyte lineage, marked by sustained expression of the oligodendrocyte transcription factor Olig2, which represses the interneuron transcription factor Dlx2. Here we show that misexpression of Dlx2 alone in postnatal mouse OPCs caused them to switch their fate to GABAergic neurons within 2 days by downregulating Olig2 and upregulating a network of inhibitory neuron transcripts. After two weeks, some OPC-derived neurons generated trains of action potentials and formed clusters of GABAergic synaptic proteins. Our study revealed that the developmental molecular logic can be applied to promote neuronal reprogramming from OPCs.
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影响因子：
9.8
作者：
Heinrich C;Blum R;Gascón S;Masserdotti G;Tripathi P;Sánchez R;Tiedt S;Schroeder T;Götz M;Berninger B
通讯作者：
Berninger B
影响因子：
8.8
作者：
Denaxa M;Kalaitzidou M;Garefalaki A;Achimastou A;Lasrado R;Maes T;Pachnis V
通讯作者：
Pachnis V
DOI：
10.1523/jneurosci.3583-12.2012
发表时间：
2012-12-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Close J;Xu H;De Marco García N;Batista-Brito R;Rossignol E;Rudy B;Fishell G
通讯作者：
Fishell G
影响因子：
4.8
作者：
Dobashi, Y;Shoji, M;Kameya, T
通讯作者：
Kameya, T
影响因子：
14.8
作者：
Kaech, Stefanie;Banker, Gary
通讯作者：
Banker, Gary