Longterm quiescent cells in the aged human subventricular neurogenic system specifically express GFAP-δ

A main neurogenic niche in the adult human brain is the subventricular zone (SVZ). Recent data suggest that the progenitors that are born in the human SVZ migrate via the rostral migratory stream (RMS) towards the olfactory bulb (OB), similar to what has been observed in other mammals. A subpopulation of astrocytes in the SVZ specifically expresses an assembly-compromised isoform of the intermediate filament protein glial fibrillary acidic protein (GFAP-δ). To further define the phenotype of these GFAP-δ expressing cells and to determine whether these cells are present throughout the human subventricular neurogenic system, we analysed SVZ, RMS and OB sections of 14 aged brain donors (ages 74-93). GFAP-δ was expressed in the SVZ along the ventricle, in the RMS and in the OB. The GFAP-δ cells in the SVZ co-expressed the neural stem cell (NSC) marker nestin and the cell proliferation markers proliferating cell nuclear antigen (PCNA) and Mcm2. Furthermore, BrdU retention was found in GFAP-δ positive cells in the SVZ. In the RMS, GFAP-δ was expressed in the glial net surrounding the neuroblasts. In the OB, GFAP-δ positive cells co-expressed PCNA. We also showed that GFAP-δ cells are present in neurosphere cultures that were derived from SVZ precursors, isolated postmortem from four brain donors (ages 63-91). Taken together, our findings show that GFAP-δ is expressed in an astrocytic subpopulation in the SVZ, the RMS and the OB. Importantly, we provide the first evidence that GFAP-δ is specifically expressed in longterm quiescent cells in the human SVZ, which are reminiscent of NSCs.