Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain

Abstract

The adult CNS contains an abundant population of oligodendrocyte precursor cells (NG2+ cells) that generate oligodendrocytes and repair myelin, but how these ubiquitous progenitors maintain their density is unknown. Here we generated NG2-mEGFP mice and used in vivo two-photon imaging to study their dynamics in the adult brain. Time-lapse imaging revealed that NG2+ cells in the cortex are highly dynamic; they survey their local environment with motile filopodia, extend growth cones, and continuously migrate. They maintain unique territories through self-avoidance, and NG2+ cell loss through death, differentiation, or ablation triggered rapid migration and proliferation of adjacent cells to restore their density. NG2+ cells recruited to sites of focal CNS injury were similarly replaced by a proliferative burst surrounding the injury site. Thus, homeostatic control of NG2+ cell density through a balance of active growth and self-repulsion ensures that these progenitors are available to replace oligodendrocytes and participate in tissue repair.

Differential local tissue permissiveness influences the final fate of GPR17‐expressing oligodendrocyte precursors in two distinct models of demyelination

“…These results are in line with previous literature data showing that, after injury, OPCs enhance their pool of progenitors, are actively recruited at the sites of focal CNS injury, and rapidly migrate and proliferate to restore their density (Hughes, Kang, Fukaya, & Bergles, 2013). However, we also show that only in the cuprizone model GFP + cells do actually differentiate to mature oligodendrocytes contributing to remyelination (Figure 7f).…”

Function of neural stem cells in ischemic brain repair processes

“…68 OPCs also act as a surveillance network to detect brain injury. 69 Using a fate mapping strategy, studies demonstrate that stroke increases neural stem cell lineage OPCs and promotes these OPCs to differentiate into myelin forming oligodendrocytes in peri-infarct white matter. [49][50][51][52][53] These data suggest that OPCs generated by adult neural stem cells contribute to oligodendrogenesis after stroke.…”

Subcortical ischemic vascular disease: Roles of oligodendrocyte function in experimental models of subcortical white-matter injury

“…Microglia is accumulated in lesion area, and those microglia may ingest OPCs. 86 However, in the experimental allergic encephalomyelitis model, activated microglia could increase oligodendrogenesis. 87 The phenotypic heterogeneities in microglia may be related to the complex microglial roles on OPCs after brain injury.…”