Progenies of NG2 glia: what do we learn from transgenic mouse models ?

Abstract

In the mammalian central nervous system, nerve-glia antigen 2 (NG2) glia are considered the fourth glial population in addition to astrocytes, oligodendrocytes and microglia. The fate of NG2 glia in vivo has been carefully studied in several transgenic mouse models using the Cre/loxP strategy. There is a clear agreement that NG2 glia mainly serve as progenitors for oligodendrocytes and a subpopulation of astrocytes mainly in the ventral forebrain, whereas the existence of a neurogenic potential of NG2 glia is lack of adequate evidence. This mini review summarizes the findings from recent studies regarding the fate of NG2 glia during development. We will highlight the age-and-region-dependent heterogeneity of the NG2 glia differentiation potential. We will also discuss putative reasons for inconsistent findings in various transgenic mouse lines of previous studies.

Generation of Multipotential NG2 Progenitors From Mouse Embryonic Stem Cell-Derived Neural Stem Cells

“…Similarly, a neurogenic potential among NG2-glia has been demonstrated by in vitro fate mapping of retrovirus-labeled SVZ progenitors ( Levison and Goldman, 1997 ), and in vivo by genetic fate mapping methods ( Rivers et al, 2008 ; Guo et al, 2010 ). However, other studies using different reporter lines have failed to confirm these observations ( Zhu et al, 2008a ; Huang et al, 2014 ) and the neurogenic potential of NG2-glia remains controversial (reviewed in Guo et al, 2021 ). Notwithstanding this debate, other OPC genes, such as proteolipid protein (PLP), are associated with a neurogenic progenitor phenotype during embryonic development ( Delaunay et al, 2008 ).…”

Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease

“…Ependyma injured [72] Yes [93] Differentiation No [82] Yes [92] Yes [77] Yes [82] Yes, Low [72] Yes [93] Migration Yes, Low [84] Yes, Low [92] Yes, High [77] Yes, Low [72] Yes [93] Quiescence Yes [94] Yes [82] No Yes, High [94] Yes, Low [92] Yes, High [44] Yes, High [96] Yes, High [44] Yes, High [97] Yes, High [98] Differentiation Yes, Medium [95] Yes, Medium [89] Yes, Medium [99] Yes, Medium [44] Yes, Low [89] Yes [98] Migration Yes, Medium [95] Yes [96] Yes [44] Yes [99] Yes [98] Quiescence Yes, Low [99] Possibly [12] No [96] No [97] Decrease [100] Glial Scar Formation N/A Yes [44] Yes, 25% [45] Yes [99] Yes, 5% [45] Yes, 5-8% [45] Yes [98] Neural Lesion N/A Yes, High [96] Yes, Delayed increase…”

“…Transgenic mouse lines have been established to target NG2+ populations using promoters from PDGFRa, Olig2, and Sox10 genes; commonly expressed in NG2+ populations [69]. Approximately 80% or more cells in NG2+ populations are targeted by these factors, however in varying ratio [94]. This fact contributes to inconsistencies between published results on NG2+ populations and NSPC characterization.…”

“…This fact contributes to inconsistencies between published results on NG2+ populations and NSPC characterization. Targeted populations may not truly represent the NG2+ cells but extend to a variety of other cell types as well [94].In addition, major differences in injury models and glial scar properties contributes to controversial NG2+ stem-like nature [69]. Issues may also result from astrocyte identification methods within the glial scar border, as GFAP is the most common astrocyte marker used but is not expressed by all astrocyte subtypes.…”

Oligodendroglial GABAergic Signaling: More Than Inhibition!

“…They differentiate from precursor cells (OPCs) [ 5 – 8 ]. Despite lifelong ongoing differentiation into OLs, OPCs maintain a certain cell density due to continuous self-renewal [ 9 – 12 ]. Proliferation and differentiation of OPCs are modulated by growth factors [ 13 – 15 ], as well as by communication between OPCs and axons [ 16 – 18 ].…”