Abstract
In jawed vertebrates, oligodendrocytes (OLs) are the myelin-producing glial cells responsible for ensheathment of axons within the central nervous system and are also crucial for remyelination following injury or disease. Olig2 is a crucial factor in the specification and differentiation of oligodendrocyte precursor cells (OPCs) that give rise to mature, myelin-producing OLs in the developing and postnatal CNS; however, its role in adulthood is less well understood. To investigate the role Olig2 plays in regulating gene expression in the adult OL lineage in a physiologically-relevant context, we performed chromatin immunoprecipitation followed by next generation sequencing analysis (ChIP-Seq) using whole spinal cord tissue harvested from adult mice.We found that many of the Olig2-bound sites were associated with genes with biological processes corresponding to OL differentiation (Nkx2.2, Nkx6.2, and Sip1), myelination and ensheathment (Mbp, Cldn11, and Mobp), as well as cell cycle and cytoskeletal regulation. This suggests Olig2 continues to play a critical role in processes related to OL differentiation and myelination well into adulthood.
Highlights
Wrapping axons in myelin sheaths has evolved in jawed vertebrates, gnatostomes, and some invertebrates as a way to increase nerve conduction velocity, enabling more rapid and efficient flow of information within the nervous system [1,2]
To identify the major biological functions represented by the gene targets in our dataset, we looked for statistically overrepresented gene ontology (GO) terms related to biological processes using PANTHER (GeneOntology.org; [49])
We present findings from a Chromatin immunoprecipitation (ChIP)-Seq analysis identifying direct in vivo targets of Olig2 in the adult mouse spinal cord
Summary
Wrapping axons in myelin sheaths has evolved in jawed vertebrates, gnatostomes, and some invertebrates as a way to increase nerve conduction velocity, enabling more rapid and efficient flow of information within the nervous system [1,2]. In the CNS, myelin is produced by OLs, making these glia cells indispensable for proper neuronal function and neural information processing. The importance of axon ensheathment is illustrated by the severe loss of function associated with demyelination following spinal cord injury or in demyelinating disorders like multiple sclerosis (MS), leukodystrophies, and peripheral demyelinating diseases [3,4,5]. Understanding the complex gene regulatory networks underlying myelin production and remyelination within the adult CNS is essential for developing future regenerative therapies.
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