Oligodendroglia heterogeneity in the human central nervous system

Abstract

It is the centenary of the discovery of oligodendrocytes and we are increasingly aware of their importance in the functioning of the brain in development, adult learning, normal ageing and in disease across the life course, even in those diseases classically thought of as neuronal. This has sparked more interest in oligodendroglia for potential therapeutics for many neurodegenerative/neurodevelopmental diseases due to their more tractable nature as a renewable cell in the central nervous system. However, oligodendroglia are not all the same. Even from the first description, differences in morphology were described between the cells. With advancing techniques to describe these differences in human tissue, the complexity of oligodendroglia is being discovered, indicating apparent functional differences which may be of critical importance in determining vulnerability and response to disease, and targeting of potential therapeutics. It is timely to review the progress we have made in discovering and understanding oligodendroglial heterogeneity in health and neuropathology.

A population of gray matter oligodendrocytes directly associates with the vasculature

“…Oligodendrocytes are heterogeneous (reviewed in Seeker and Williams, 2021) and can be classified based on their developmental origin (Kessaris et al, 2006), transcriptomic status (Floriddia et al, 2020; Marques et al, 2016), anatomical organization (del Rio Hortega, 1928; Floriddia et al, 2020; Peters et al, 1991; Takasaki et al, 2010) or functional impact (Battefeld et al, 2016). Whether the population of vOLs has distinct functional properties remains to be addressed in future functional studies.…”

Single-cell transcriptomics of resected human traumatic brain injury tissues reveals acute activation of endogenous retroviruses in oligodendroglia

“…Myelinating oligodendrocytes are essential for saltatory nerve conduction in the central nervous system and are involved in the metabolic support of neurons and the modulation of neuronal excitability 11 . There is also emerging evidence that brain oligodendrocytes are morphologically and transcriptionally heterogeneous, and that their functional role may be altered in disease 12,13 . The neuroinflammatory response occurring after TBI seems to be associated with oligodendrocyte vulnerability 9 , and persistent neuroinflammation is often found in atrophied white matter tracts of long-term TBI survivors 2 .…”

Editorial: The Role of Astroglia and Oligodendroglia in CNS Development, Plasticity, and Disease – Novel Tools and Investigative Approaches

“…Astroglia support synaptogenesis and synapse plasticity, whereas oligodendroglia assure developmental myelination, sustain axon maturation and integrity, and plastically respond to experience with de-novo myelin deposition or remodeling (Verkhratsky and Nedergaard, 2018 ; Kuhn et al, 2019 ). Studies have also provided evidence of a remarkable level of functional, molecular and developmental heterogeneity (Marques et al, 2016 ; Cerrato et al, 2018 ; Khakh and Deneen, 2019 ; Batiuk et al, 2020 ; Sherafat et al, 2021 ; Seeker and Williams, 2022 ) and unexpected interactions with immune cells (including microglia, peripheral macrophages, and T cells) for both astrocytes and oligodendroglia (Ponath et al, 2018 ; Kirby and Castelo-Branco, 2021 ). This latter aspect contributes to astro-/oligodendroglia response to injury.…”