The Chromatin Environment Around Interneuron Genes in Oligodendrocyte Precursor Cells and Their Potential for Interneuron Reprograming.

Q. Richard Lu,Jia Liu,Chuntao Zhao,Linda L. Boshans,Akiko Nishiyama,Paul J. Tesar,Daniel C. Factor,Ion Mandoiu,Vijender Singh,Patrizia Casaccia

doi:10.3389/fnins.2019.00829

Abstract

Oligodendrocyte precursor cells (OPCs), also known as NG2 glia, arise from neural progenitor cells in the embryonic ganglionic eminences that also generate inhibitory neurons. They are ubiquitously distributed in the central nervous system, remain proliferative through life, and generate oligodendrocytes in both gray and white matter. OPCs exhibit some lineage plasticity, and attempts have been made to reprogram them into neurons, with varying degrees of success. However, little is known about how epigenetic mechanisms affect the ability of OPCs to undergo fate switch and whether OPCs have a unique chromatin environment around neuronal genes that might contribute to their lineage plasticity. Our bioinformatic analysis of histone posttranslational modifications at interneuron genes in OPCs revealed that OPCs had significantly fewer bivalent and repressive histone marks at interneuron genes compared to astrocytes or fibroblasts. Conversely, OPCs had a greater degree of deposition of active histone modifications at bivalently marked interneuron genes than other cell types, and this was correlated with higher expression levels of these genes in OPCs. Furthermore, a significantly higher proportion of interneuron genes in OPCs than in other cell types lacked the histone posttranslational modifications examined. These genes had a moderately high level of expression, suggesting that the “no mark” interneuron genes could be in a transcriptionally “poised” or “transitional” state. Thus, our findings suggest that OPCs have a unique histone code at their interneuron genes that may obviate the need for erasure of repressive marks during their fate switch to inhibitory neurons.

Highlights

Oligodendrocyte precursor cells (OPCs), known as NG2 glia, NG2 cells, or polydendrocytes, are ubiquitously present throughout the central nervous system and comprise 2-9% of total cells (Dawson et al, 2003)
Since OPCs share an early developmental origin with cortical interneurons, we sought to determine whether OPCs had specific histone post-translational modifications at interneuron genes, which might facilitate their conversion into interneurons
We focused this study on examining histone PTMs at interneuron genes in OPCs as a first step toward gaining a mechanistic insight into how OPCs can be reprogramed toward an interneuron fate

Summary

Introduction

Oligodendrocyte precursor cells (OPCs), known as NG2 glia, NG2 cells, or polydendrocytes, are ubiquitously present throughout the central nervous system and comprise 2-9% of total cells (Dawson et al, 2003). They represent a fourth major population of glial cells endowed with proliferative and selfrenewing ability throughout life. Their most well known function is to generate oligodendrocytes in the developing and mature central nervous system, but they exhibit some degree of lineage plasticity, as briefly reviewed below. It has become the convention to identify OPCs by the combinatorial expression of the oligodendrocyte transcription factor Olig (see below) and one of the two cell surface antigens, NG2 or PDGFRα

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Conclusion