Transcriptional and Epigenetic Regulation of Oligodendrocyte Development and Myelination in the Central Nervous System

Abstract

Central nervous system (CNS) myelination by oligodendrocytes (OLs) is a highly orchestrated process involving well-defined steps from specification of neural stem cells into proliferative OL precursors followed by terminal differentiation and subsequent maturation of these precursors into myelinating OLs. These specification and differentiation processes are mediated by profound global changes in gene expression, which are in turn subject to control by both extracellular signals and regulatory networks intrinsic to the OL lineage. Recently, basic transcriptional mechanisms that control OL differentiation and myelination have begun to be elucidated at the molecular level and on a genome scale. The interplay between transcription factors activated by differentiation-promoting signals and master regulators likely exerts a crucial role in controlling stage-specific progression of the OL lineage. In this review, we describe the current state of knowledge regarding the transcription factors and the epigenetic programs including histone methylation, acetylation, chromatin remodeling, micro-RNAs, and noncoding RNAs that regulate development of OLs and myelination.

Single-Cell RNA-Seq Reveals Hypothalamic Cell Diversity

“…The four Oligo1 + oligodendrocyte clusters could be further distinguished from each other by the expression of Top2a (proliferating oligodendrocyte precursor cell [POPC]), Pdgfra (oligodendrocyte precursor cell [OPC]), Fyn (newly formed oligodendrocyte [NFO]), and Mobp (myelinating oligodendrocyte [MO]) (Figures 2A and 2B). These subtypes reflect distinct stages of oligodendrocyte differentiation (Emery and Lu, 2015). The three Sox9 + cell clusters could also be distinguished from one another by subtype markers Agt (astrocytes [Astro]), Ccdc153 (ependymocyte [Ependy]), and Rax (tanycyte [Tany]) (Figures 2A and 2B).…”

Oligodendrocyte Development and Plasticity

“…The balance of evidence now suggests that Olig1 is dispensable for OL development and myelination , although it appears to be needed for remyelination of demyelinated lesions in the adult CNS (Arnett et al 2004; also see Emery and Lu 2015).…”

How to make an oligodendrocyte

“…As OPCs transition to postmitotic oligodendrocytes, they undergo dramatic chromatin condensation with heterochromatin formation (Huang et al, 2015), which is associated with the silencing of many genes involved in their proliferative response to mitogenic cues, including Wnt, FGF and PDGF (Barca-Mayo and Yu et al, 2010), as well as that of their upstream regulator MYC (Magri et al, 2014). Yet despite chromatin condensation, Olig2 and Sox10 expression continues, and serves not only to direct oligodendrocyte fate commitment (Liu et al, 2007;Xin et al, 2005), but also to consolidate phenotype by recruiting chromatin remodelers to oligodendrocyte-specific enhancers (Weider et al, 2013;Yu et al, 2013;Emery and Lu, 2015).…”