A Clonal NG2-Glia Cell Response in a Mouse Model of Multiple Sclerosis

Abstract

NG2-glia, also known as oligodendrocyte precursor cells (OPCs), have the potential to generate new mature oligodendrocytes and thus, to contribute to tissue repair in demyelinating diseases like multiple sclerosis (MS). Once activated in response to brain damage, NG2-glial cells proliferate, and they acquire a reactive phenotype and a heterogeneous appearance. Here, we set out to investigate the distribution and phenotypic diversity of NG2-glia relative to their ontogenic origin, and whether there is a clonal NG2-glial response to lesion in an experimental autoimmune encephalomyelitis (EAE) murine model of MS. As such, we performed in utero electroporation of the genomic lineage tracer, StarTrack, to follow the fate of NG2-glia derived from single progenitors and to evaluate their response to brain damage after EAE induction. We then analyzed the dispersion of the NG2-glia derived clonally from single pallial progenitors in the brain of EAE mice. In addition, we examined several morphological parameters to assess the degree of NG2-glia reactivity in clonally-related cells. Our results reveal the heterogeneity of these progenitors and their cell progeny in a scenario of autoimmune demyelination, revealing the ontogenic phenomena at play in these processes.

Multicolor strategies for investigating clonal expansion and tissue plasticity

“…However, mixed clones formed by reactive and non-reactive sibling cells were also described, suggesting that astrocyte response diversity is both developmentally established and regulated by the molecular environment [ 148 ]. In addition, the response of NG2-glial clones derived from embryonic GFAP-positive progenitor cells to EAE lesions has been addressed by recycling these previous animals and tissues [ 149 ]. In inflammatory and lesioned mouse cortex, NG2-glial clones were spatially distributed in different areas and most of them were located in the lower cortical layers [ 149 ].…”

“…In addition, the response of NG2-glial clones derived from embryonic GFAP-positive progenitor cells to EAE lesions has been addressed by recycling these previous animals and tissues [ 149 ]. In inflammatory and lesioned mouse cortex, NG2-glial clones were spatially distributed in different areas and most of them were located in the lower cortical layers [ 149 ]. Similar morphological diversities were observed for NG2-glia and GFAP clones after both mechanical and demyelinating damages.…”

The 5-HT and PLC Signaling Pathways Regulate the Secretion of IL-1β, TNF-α and BDNF from NG2 Cells

“…e occurrence of this e ect is orchestrated by Glu signal transduction initiated by neurons. is relationship suggests that the excitability of the central nervous system in uences the proliferation and differentiation of NG2 cells [29,30]. Activated NG2 cells secrete substances that a ect the activity of neurons and glial cells [31,32].…”

Lineage Relationships Between Subpallial Progenitors and Glial Cells in the Piriform Cortex

“…Moreover, sibling astrocytes showed preferential gap-junction coupling compared to non-related astrocytes ( Gutiérrez et al, 2019 ). This coupled response between sibling cells may be implicated in physiological and pathological conditions ( Martín-López et al, 2013 ; Bribián et al, 2018 ; Barriola et al, 2020 ). Therefore, this data reinforces the idea of the high heterogeneity of these neural cells at a morphological, functional, and genetic level.…”