Extrinsic Factors Driving Oligodendrocyte Lineage Cell Progression in CNS Development and Injury

Baydyuk, Maryna; Morrison, Vivianne E.; Gross, Phillip S.; Huang, Jeffrey K.

doi:10.1007/s11064-020-02967-7

Cited by 26 publications

(19 citation statements)

References 182 publications

(254 reference statements)

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“…During CNS development, OL progenitor cells (OPCs) are generated from neural stem/progenitor cells (NSPCs) in several regions in a precise spatiotemporal manner [ 3 , 4 ]. Multiple transcriptional regulators cooperate to orchestrate changes in gene expression leading to OPC fate selection and subsequent differentiation into OL.…”

Section: Introductionmentioning

confidence: 99%

Ion Channels as New Attractive Targets to Improve Re-Myelination Processes in the Brain

Cherchi

Bulli

Venturini

et al. 2021

IJMS

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Multiple sclerosis (MS) is the most demyelinating disease of the central nervous system (CNS) characterized by neuroinflammation. Oligodendrocyte progenitor cells (OPCs) are cycling cells in the developing and adult CNS that, under demyelinating conditions, migrate to the site of lesions and differentiate into mature oligodendrocytes to remyelinate damaged axons. However, this process fails during disease chronicization due to impaired OPC differentiation. Moreover, OPCs are crucial players in neuro-glial communication as they receive synaptic inputs from neurons and express ion channels and neurotransmitter/neuromodulator receptors that control their maturation. Ion channels are recognized as attractive therapeutic targets, and indeed ligand-gated and voltage-gated channels can both be found among the top five pharmaceutical target groups of FDA-approved agents. Their modulation ameliorates some of the symptoms of MS and improves the outcome of related animal models. However, the exact mechanism of action of ion-channel targeting compounds is often still unclear due to the wide expression of these channels on neurons, glia, and infiltrating immune cells. The present review summarizes recent findings in the field to get further insights into physio-pathophysiological processes and possible therapeutic mechanisms of drug actions.

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Section: Introductionmentioning

confidence: 99%

Ion Channels as New Attractive Targets to Improve Re-Myelination Processes in the Brain

Cherchi

Bulli

Venturini

et al. 2021

IJMS

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“…Neuronal activity, even that caused by epileptic seizures, can in fact induce myelination (Gibson et al, 2014, Mensch et al, 2015, Marisca et al, 2020, Hughes and Appel, 2020. Microglia and astrocytes interact with and regulate the membrane processes of oligodendrocytes, thereby shaping, maintaining and repairing myelin (reviewed by Baydyuk et al, 2020, Traiffort et al, 2020, de Waard and Bugiani, 2020. Therefore, to thoroughly understand the functions of microglia in myelination and myelin health, one should examine their dynamic interactions with oligodendrocytes and astrocytes.…”

Section: Box 1 Glial Cells: the Pillars Of White Matter Integritymentioning

confidence: 99%

“…Astrocytes can secrete cytokines and growth factors that influence myelination by regulating OPC survival, oligodendrocyte differentiation and maturation (Lanciotti et al, 2013, Lundgaard et al, 2014, Baydyuk et al, 2020, Traiffort et al, 2020. Besides communication via soluble factors, direct cell-cell contacts in the form of gap junctions, formed by connexins, provide oligodendrocytes, but also neurons and axons, with lipids and glucose as both an energy supply and as substrates for myelination (Orthmann-Murphy et al, 2008, Camargo et al, 2017.…”

Section: Box 1 Glial Cells: the Pillars Of White Matter Integritymentioning

confidence: 99%

The multicellular interplay of microglia in health and disease: lessons from leukodystrophy

Berdowski

Sanderson

Ham

2021

Disease Models &Amp; Mechanisms

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Microglia are highly dynamic cells crucial for developing and maintaining lifelong brain function and health through their many interactions with essentially all cellular components of the central nervous system. The frequent connection of microglia to leukodystrophies, genetic disorders of the white matter, has highlighted their involvement in the maintenance of white matter integrity. However, the mechanisms that underlie their putative roles in these processes remain largely uncharacterized. Microglia have also been gaining attention as possible therapeutic targets for many neurological conditions, increasing the demand to understand their broad spectrum of functions and the impact of their dysregulation. In this Review, we compare the pathological features of two groups of genetic leukodystrophies: those in which microglial dysfunction holds a central role, termed ‘microgliopathies’, and those in which lysosomal or peroxisomal defects are considered to be the primary driver. The latter are suspected to have notable microglia involvement, as some affected individuals benefit from microglia-replenishing therapy. Based on overlapping pathology, we discuss multiple ways through which aberrant microglia could lead to white matter defects and brain dysfunction. We propose that the study of leukodystrophies, and their extensively multicellular pathology, will benefit from complementing analyses of human patient material with the examination of cellular dynamics in vivo using animal models, such as zebrafish. Together, this will yield important insight into the cell biological mechanisms of microglial impact in the central nervous system, particularly in the development and maintenance of myelin, that will facilitate the development of new, and refinement of existing, therapeutic options for a range of brain diseases.

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“…OPC-derived interleukin-33 (IL-33) has also been shown to regulate the differentiation of OLs to mature OLs in vitro , by lentivirus-mediated knock-down experiments resulting in a down-regulation of OL differentiation genes, and in vivo , by analyzing IL-33 null mice which revealed defective myelination in the corpus callosum (Sung et al, 2019 ). Cells of the OPC lineage are also influenced by other systemic or environmental changes (ageing, inflammation or hypoxia; for review: Baydyuk et al, 2020 ). Extrinsic factors also include different cell types with which cells of the OPC lineage are in contact (neurons, astrocytes, blood vessels and microglia), some of which were manipulated by genetic alteration while other evidence came from co-culture in vitro experiments (for review: Baydyuk et al, 2020 ).…”

Section: Genetic Technologiesmentioning

confidence: 99%

“…Cells of the OPC lineage are also influenced by other systemic or environmental changes (ageing, inflammation or hypoxia; for review: Baydyuk et al, 2020 ). Extrinsic factors also include different cell types with which cells of the OPC lineage are in contact (neurons, astrocytes, blood vessels and microglia), some of which were manipulated by genetic alteration while other evidence came from co-culture in vitro experiments (for review: Baydyuk et al, 2020 ).…”

Section: Genetic Technologiesmentioning

confidence: 99%

Novel Tools and Investigative Approaches for the Study of Oligodendrocyte Precursor Cells (NG2-Glia) in CNS Development and Disease

Galichet

Clayton

Lovell‐Badge

2021

Front. Cell. Neurosci.

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Oligodendrocyte progenitor cells (OPCs), also referred to as NG2-glia, are the most proliferative cell type in the adult central nervous system. While the primary role of OPCs is to serve as progenitors for oligodendrocytes, in recent years, it has become increasingly clear that OPCs fulfil a number of other functions. Indeed, independent of their role as stem cells, it is evident that OPCs can regulate the metabolic environment, directly interact with and modulate neuronal function, maintain the blood brain barrier (BBB) and regulate inflammation. In this review article, we discuss the state-of-the-art tools and investigative approaches being used to characterize the biology and function of OPCs. From functional genetic investigation to single cell sequencing and from lineage tracing to functional imaging, we discuss the important discoveries uncovered by these techniques, such as functional and spatial OPC heterogeneity, novel OPC marker genes, the interaction of OPCs with other cells types, and how OPCs integrate and respond to signals from neighboring cells. Finally, we review the use of in vitro assay to assess OPC functions. These methodologies promise to lead to ever greater understanding of this enigmatic cell type, which in turn will shed light on the pathogenesis and potential treatment strategies for a number of diseases, such as multiple sclerosis (MS) and gliomas.

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Extrinsic Factors Driving Oligodendrocyte Lineage Cell Progression in CNS Development and Injury

Cited by 26 publications

References 182 publications

Ion Channels as New Attractive Targets to Improve Re-Myelination Processes in the Brain

Ion Channels as New Attractive Targets to Improve Re-Myelination Processes in the Brain

The multicellular interplay of microglia in health and disease: lessons from leukodystrophy

Novel Tools and Investigative Approaches for the Study of Oligodendrocyte Precursor Cells (NG2-Glia) in CNS Development and Disease

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