Circumventricular organs: a novel site of neural stem cells in the adult brain.
Neurogenesis in the adult mammalian nervous system is now well established in the subventricular zone of the anterolateral ventricle and subgranular zone of the hippocampus. In these regions, neurons are thought to arise from neural stem cells, identified by their expression of specific intermediate filament proteins (nestin, vimentin, GFAP) and transcription factors (Sox2). In the present study, we show that in adult rat and mouse, the circumventricular organs (CVOs) are rich in nestin+, GFAP+, vimentin+ cells which express Sox2 and the cell cycle-regulating protein Ki67. In culture, these cells proliferate as neurospheres and express neuronal (doublecortin+, beta-tubulin III+) and glial (S100beta+, GFAP+, RIP+) phenotypic traits. Further, our in vivo studies using bromodeoxyuridine show that CVO cells proliferate and undergo constitutive neurogenesis and gliogenesis. These findings suggest that CVOs may constitute a heretofore unknown source of stem/progenitor cells, capable of giving rise to new neurons and/or glia in the adult brain.
Bennett
Lori
L
Farber Institute for Neurosciences, Department of Neurology, Thomas Jefferson University Medical College, 900 Walnut Street, Philadelphia, PA 19107, USA.
Yang
Ming
M
Enikolopov
Grigori
G
Iacovitti
Lorraine
L
D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D049109:Cell Proliferation; D000089662:Doublecortin Protein; D005260:Female; D020546:Fourth Ventricle / Q000166:cytology* / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D007381:Intermediate Filament Proteins / Q000096:biosynthesis; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D064231:Nestin; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051381:Rats; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis; D020542:Third Ventricle / Q000166:cytology* / Q000378:metabolism; D014746:Vimentin / Q000096:biosynthesis
D015415:Biomarkers; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; D055748:SOXB1 Transcription Factors; D014746:Vimentin