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Human neurospheres derived from the fetal central nervous system are regionally and temporally specified but are not committed

 Hyoung-Tai Kim  ;  Il-Sun Kim  ;  Il-Shin Lee  ;  Jean-Pyo Lee  ;  Evan Y. Snyder  ;  Kook In Park 
 EXPERIMENTAL NEUROLOGY, Vol.199(1) : 222-235, 2006 
Journal Title
Issue Date
Animals ; Blotting, Northern/methods ; Cell Count/methods ; Cell Differentiation/physiology* ; Cells, Cultured ; Central Nervous System/cytology* ; Central Nervous System/embryology ; Coculture Techniques/methods ; Fetus ; Gene Expression/physiology ; Humans ; Immunohistochemistry/methods ; Indoles ; Mice ; Nerve Tissue Proteins/metabolism* ; Neurons/physiology* ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction/methods ; Stem Cells/physiology* ; Time Factors
Human neurospheres ; Neural stem cells ; Neural progenitors ; Region-specific genes ; Differentiation
Proliferating single cells were isolated from various CNS regions (telencephalon, diencephalon, midbrain, cerebellum, pons and medulla, and spinal cord) of human fetal cadavers at 13 weeks of gestation and grown as neurospheres in long-term cultures. We investigated whether neural stem cells (NSCs) or progenitors within spheres have specific regional or temporal characteristics with regard to growth, differentiation, and region-specific gene expression, and whether these molecular specifications are reversible. Regardless of regional origin, all of the neurospheres were found to contain cells of different subtypes, which suggests that multipotent NSCs, progenitors or radial glial cells co-exist with restricted neuronal or glial progenitors within the neurospheres. Neurospheres from the forebrain grew faster and gave rise to significantly more neurons than did those from either the midbrain or hindbrain, and regional differences in neuronal differentiation appeared to be sustained during long-term passage of neurospheres in culture. There was also a trend towards a reduction in neuronal emergence from the respective neurospheres over time in culture, although the percentages of neurons generated from cerebellum-derived neurospheres increased dramatically. These results suggest that differences in neuronal differentiation for the various neurospheres are spatially and temporally determined. In addition, the properties of glial fibrillary acidic protein (GFAP)-, glutamate-, and γ-aminobutyric acid (GABA)-expressing cells derived from neurospheres of the respective CNS regions appear to be regionally and temporally different. Isolated human neurospheres from different CNS compartments expressed distinctive molecular markers of regional identity and maintained these patterns of region-specific gene expression during long-term passage in vitro. To determine the potential of human neurospheres for regional fate plasticity, single spheres from the respective regions were co-cultured with embryonic day 16.5 (E16.5 d) mouse brain slices. Specific cues from the developing mouse brain tissues induced the human neurospheres to express different marker genes of regional identity and to suppress the expression of their original marker genes. Thus, even the early regional identities of human neurospheres may not be irreversible and may be altered by local inductive cues. These findings have important implications for understanding the characteristics of growth, differentiation, and molecular specification of human neurospheres derived from the developing CNS, as well as the therapeutic potential for neural repair.
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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Il-Sun(김일선) ORCID logo https://orcid.org/0000-0003-4033-4323
Park, Kook In(박국인) ORCID logo https://orcid.org/0000-0001-8499-9293
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