Oligodendrocyte progenitors as environmental biosensors

Abstract

The past decade has seen an important revision of the traditional concept of the role and function of glial cells. From "passive support" for neurons, oligodendrocyte lineage cells are now recognized as metabolic exchangers with neurons, a cellular interface with blood vessels and responders to gut-derived metabolites or changes in the social environment. In the developing brain, the differentiation of neonatal oligodendrocyte progenitors (nOPCs) is required for normal brain function. In adulthood, the differentiation of adult OPCs (aOPCs) serves an important role in learning, behavioral adaptation and response to myelin injury. Here, we propose the concept of OPCs as environmental biosensors, which "sense" chemical and physical stimuli over time and adjust to the new challenges by modifying their epigenome and consequent transcriptome. Because epigenetics defines the ability of the cell to "adapt" gene expression to changes in the environment, we propose a model of OPC differentiation resulting from time-dependent changes of the epigenomic landscape in response to declining mitogens, raising hormone levels, neuronal activity, changes in space constraints or stiffness of the extracellular matrix. We propose that the intrinsically different functional properties of aOPCs compared to nOPCs result from the accrual of "epigenetic memories" of distinct events, which are "recorded" in the nuclei of OPCs as histone and DNA marks, defining a "unique epigenomic landscape" over time.

Keywords: Aging; Brain; Chromatin; DNA methylation; Epigenetics; Histone.