Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA.
Department of Computer Science and Engineering, University of Connecticut, Storrs, CT, USA.
Sci Rep. 2021 Feb 11;11(1):3552. doi: 10.1038/s41598-021-82931-9.
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.
少突胶质前体细胞（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，可在整个生命周期中产生髓鞘少突胶质细胞。新皮层中的少突胶质前体细胞亚群来源于胚胎神经节隆起中的祖细胞，这些祖细胞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确定，因为它们成为少突胶质细胞谱系的一部分，这一过程的标志是少突胶质细胞转录因子 Olig2 的持续表达，该基因抑制中间神经元转录因子 Dlx2。本文研究表明，在出生后小鼠的少突胶质前体细胞中单独过表达 Dlx2，可在 2 天内通过下调 Olig2 和上调抑制性神经元转录本网络，促使它们的命运向 GABA 能神经元转变。两周后，一些少突胶质前体细胞衍生的神经元产生动作电位串，并形成 GABA 能突触蛋白簇。本研究揭示了发育分子逻辑可用于促进少突胶质前体细胞的神经元重编程。
