title: The adult spinal cord harbors a population of GFAP-positive progenitors with limited self-renewal potential.
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.
authors.affiliation: Brain Research Institute, University of Zurich/ETHZ, Switzerland.
authors.forename: Roberto
authors.initials: R
authors.lastname: Fiorelli
authors.forename: Arantxa
authors.initials: A
authors.lastname: Cebrian-Silla
authors.forename: Jose-Manuel
authors.initials: JM
authors.lastname: Garcia-Verdugo
authors.forename: Olivier
authors.initials: O
authors.lastname: Raineteau
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C528900:glial fibrillary astrocytic protein, mouse
keywords: SVZ; astrocytes; ependymal cells; neural stem cells; spinal cord injury