GFAP Delta as Divergent Marker of Human Glial Progenitors

Abstract

Background: Human Neural Stem Cells (hNSCs) are responsible for brain development at prenatal and postnatal stages and for tissue homeostasis and repair after injury on adulthood. The identification of hNSC specific markers is still a debated argument. GFAP-δ, the delta isoform of Glial Fibrillary Acidic Protein (GFAP), is particularly expressed in the Subventricular Zone (SVZ) of the brain and its expression has been related to long-term quiescent NSC. On the other hand, another cytoskeletal protein, gelsolin, is expressed in Neural Progenitor Cells (NPCs) migrating from the SVZ. Methods: In this study, we intended to investigate by immunocytochemistry the co-expression of GFAP-δ and gelsolin in different sources of hNSCs, and hNPCs, with particular emphasis on Good Manifacture Procedures (GMPs) grade hNSC currently used in two clinical trials on Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) patients. Results: We found that the two proteins are co-expressed by undifferentiated GFAP+ cells but tend to localize in different sub-cellular compartments and to segregate in divergent GFAP+ progenies along with differentiation. Interestingly, we proved that, after transplantation into the brain of rodent models of focal demyelination or transient global ischemia, hNSC integrating in the SVZ still retain the co-expression of GFAP-δ and gelsolin, indicating that hNSC intrinsically co-express the two proteins at the stem stage. Conclusion: These findings suggest that GFAP-δ and gelsolin may represent two candidate markers to distinguish NSC from NSC-deriving divergent astroglial phenotypes.

Prenatal ethanol exposure impairs the formation of radial glial fibers and promotes the transformation of GFAPδ‑positive radial glial cells into astrocytes

“…Moreover, GFAPδ expression is limited to specialized astrocyte populations and is more abundant in neurogenic regions, such as the SVZ of the lateral ventricle, the rostral migratory stream, the SGZ of the hippocampus and the subpial astrocytes ( 39 , 41 , 55 , 56 ). GFAPδ positive cells are specifically restricted to these neurogenic areas, where expression of Nestin and Vimentin is also observed, suggesting that GFAPδ may be a RGC-specific filament protein that is required for their substrate functions and may be a determining factor associated with neurogenesis ( 55 , 60 ). The ratio of GFAPα and GFAPδ is an important factor in the formation of the intermediate filament network, which is closely associated with cellular functions (such as neurogenesis) or cellular morphology (such as gliosis) ( 56 ).…”

Troxerutin flavonoid has neuroprotective properties and increases neurite outgrowth and migration of neural stem cells from the subventricular zone

“…There exists a class of NSCs which co-express nestin and the reactive glial cell marker GFAP. So both Nestin and GFAP are considered as NSCs markers [60]. NSCs which co-express Nestin and GFAP comprise of radial glial cells which present neural stem cell properties [61,62].…”