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

Abstract

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.

The NG2-glia is a potential target to maintain the integrity of neurovascular unit after acute ischemic stroke

“…With novel tools and investigative methodologies becoming increasingly available, more and more novel roles of NG2-glia are expected to be revealed in CNS development and diseases- (Galichet et al, 2021). Current accumulated evidence showing a critical role for NG2glia in the integrity of the NVU, supports the notion that NG2-glia is a key therapeutic target to reduce AIS-induced injury and promote repair.…”

Role of Oligodendrocyte Lineage Cells in Multiple System Atrophy

“…During development, OPCs expressing proteoglycan nerve glial antigen (NG2) differentiate into myelinating oligodendrocytes [28]. However, a pool of OPCs, comprising 5-8% of total glial cells, remain undifferentiated in the adult CNS and retain the ability to generate mature oligodendrocytes [35][36][37][38]. Although myelination and remyelination by mature oligodendrocytes are efficient in young adults, the efficiency of myelination declines dramatically with aging [39].…”

“…They are evenly distributed in the gray and white matter of the developing and adult brains [46]. OPCs are the most proliferative cell type during homeostasis and pathological conditions [36][37][38].…”

The Properties and Functions of Glial Cell Types of the Hypothalamic Median Eminence

“…For example, a role in the leptin system has been described for tanycytes ( 8 , 11 , 26 ), OPCs ( 3 ) and microglia ( 3 , 15 ), and it seems likely that differentiating OPCs and oligodendrocytes have a role to play here as well, by maintaining the ECM composition of the ME ( 12 ). Future research must use a holistic approach that investigates not only glial-neuronal interactions but also glia-glia interactions, and a wide-range of genetic and experimental tools are available to study the biology of glia both in vivo and in vitro ( 72 ).…”