Abstract
Adult neural stem cells (aNSCs) of the forebrain are GFAP-expressing cells that are intercalated within ependymal cells of the subventricular zone (SVZ). Cells showing NSCs characteristics in vitro can also be isolated from the periaqueductal region in the adult spinal cord (SC), but contradicting results exist concerning their glial versus ependymal identity. We used an inducible transgenic mouse line (hGFAP-CreERT2) to conditionally label GFAP-expressing cells in the adult SVZ and SC periaqueduct, and directly and systematically compared their self-renewal and multipotential properties in vitro. We demonstrate that a population of GFAP(+) cells that share the morphology and the antigenic properties of SVZ-NSCs mostly reside in the dorsal aspect of the central canal (CC) throughout the spinal cord. These cells are non-proliferative in the intact spinal cord, but incorporate the S-phase marker EdU following spinal cord injury. Multipotent, clonal YFP-expressing neurospheres (i.e., deriving from recombined GFAP-expressing cells) were successfully obtained from both the intact and injured spinal cord. These spheres however showed limited self-renewal properties when compared with SVZ-neurospheres, even after spinal cord injury. Altogether, these results demonstrate that significant differences exist in NSCs lineages between neurogenic and non-neurogenic regions of the adult CNS. Thus, although we confirm that a population of multipotent GFAP(+) cells co-exists alongside with multipotent ependymal cells within the adult SC, we identify these cells as multipotent progenitors showing limited self-renewal properties.
Highlights
During the development of the vertebrate central nervous system (CNS), peri-ventricular radial glial (RG) cells self-renew through asymmetric division and sequentially give rise to neurons, ependymal cells, and glial cells throughout the brain (Anthony et al, 2004; Kriegstein and AlvarezBuylla, 2009)
Lineage tracing studies at perinatal stages have revealed that RG transform into Adult neural stem cells (aNSCs) that persist within the subventricular zone (SVZ) of the lateral ventricle and produce new neurons and glia throughout adulthood (Doetsch et al, 1999; Ganat et al, 2006; Lledo et al, 2008; Merkle et al, 2004)
We confirmed the reliability of the hGFAPCreRT2 mouse line with previously reported observations by analyzing the forebrain of this mouse line at different time points (i.e., 1, 10, and 30 days) following tamoxifen administration
Summary
During the development of the vertebrate central nervous system (CNS), peri-ventricular radial glial (RG) cells self-renew through asymmetric division and sequentially give rise to neurons, ependymal cells, and glial cells throughout the brain (Anthony et al, 2004; Kriegstein and AlvarezBuylla, 2009). Lineage tracing studies at perinatal stages have revealed that RG transform into aNSCs that persist within the subventricular zone (SVZ) of the lateral ventricle and produce new neurons and glia throughout adulthood (Doetsch et al, 1999; Ganat et al, 2006; Lledo et al, 2008; Merkle et al, 2004) These adult neurogenic NSCs retain a number of radial glia properties, such as an expression of Glial Fibrillary Acidic Protein (GFAP), Nestin, Vimentin, and BLBP (Doetsch et al, 1999) and the presence of an apical process contacting the lumen of the ventricle opposing a longer basal process (Mirzadeh et al, 2008). SC-derived neurospheres show in vitro multipotency and self-renewal properties identical to cultures
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