Abstract

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.

Details

Title
Direct reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx2
Author
Boshans, Linda L 1 ; Heun, Soh 1 ; Wood, William M 1 ; Nolan, Timothy M 1 ; Mandoiu, Ion I 2 ; Yanagawa Yuchio 3 ; Tzingounis, Anastasios V 1 ; Nishiyama Akiko 4 

 University of Connecticut, Department of Physiology and Neurobiology, Storrs, USA (GRID:grid.63054.34) (ISNI:0000 0001 0860 4915) 
 University of Connecticut, Department of Computer Science and Engineering, Storrs, USA (GRID:grid.63054.34) (ISNI:0000 0001 0860 4915); University of Connecticut, Institute for Systems Genomics, Storrs, USA (GRID:grid.63054.34) (ISNI:0000 0001 0860 4915) 
 Gunma University Graduate School of Medicine, Department of Genetic and Behavioral Neuroscience, Maebashi, Japan (GRID:grid.256642.1) (ISNI:0000 0000 9269 4097) 
 University of Connecticut, Department of Physiology and Neurobiology, Storrs, USA (GRID:grid.63054.34) (ISNI:0000 0001 0860 4915); University of Connecticut, Institute for Systems Genomics, Storrs, USA (GRID:grid.63054.34) (ISNI:0000 0001 0860 4915); University of Connecticut, The Connecticut Institute for Brain and Cognitive Sciences, Storrs, USA (GRID:grid.63054.34) (ISNI:0000 0001 0860 4915) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2488174955
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.