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Glial Commitment of Mesencephalic Neural Precursor Cells Expanded as Neurospheres Precludes Their Engagement in Niche-Dependent Dopaminergic Neurogenesis

Citation

Baizabal, JM and Cano-Martinez, A and Valencia, C and Santa-Olalla, J and Young, KM and Rietze, RL and Bartlett, PF and Covarrubias, L, Glial Commitment of Mesencephalic Neural Precursor Cells Expanded as Neurospheres Precludes Their Engagement in Niche-Dependent Dopaminergic Neurogenesis, Stem Cells and Development, 21, (7) pp. 1047-1058. ISSN 1547-3287 (2012) [Refereed Article]

Copyright Statement

Copyright 2011 Mary Ann Liebert, Inc.

DOI: doi:10.1089/scd.2011.0241

Abstract

Neural precursor cells (NPCs) with high proliferative potential are commonly expanded in vitro as neurospheres. As a population, neurosphere cells show long-term self-renewal capacity and multipotentiality in vitro. These features have led to the assumption that neurosphere cells represent an expansion of the endogenous NPCs residing within the embryonic and adult brain. If this is the case, in principle, bona-fide expansion of endogenous NPCs should not significantly affect their capacity to respond to their original niche of differentiation. To address this issue, we generated primary neurospheres from the dopaminergic niche of the ventral mesencephalon and then transplanted these cells to their original niche within mesencephalic explant cultures. Primary neurosphere cells showed poor capacity to generate dopaminergic neurons in the mesencephalic niche of dopaminergic neurogenesis. Instead, most primary neurosphere cells showed glial commitment as they differentiated into astrocytes in an exclusively neurogenic niche. Subculture of primary cells demonstrated that the neurosphere assay does not amplify niche-responsive dopaminergic progenitors. Further, neurospheres cells were largely unable to acquire the endogenous positional identity within the Nkx6.1+, Nkx2.2+, and Pax7+ domains of mesencephalic explants. Finally, we demonstrate that our observations are not specific for embryonic mesencephalic cells, as NPCs in the adult subventricular zone also showed an intrinsic fate switch from neuronal to glial potential upon neurosphere amplification. Our data suggest that neurosphere formation does not expand the endogenous neurogenic NPCs but rather promotes amplification of gliogenic precursors that do not respond to niche-derived signals of cellular specification and differentiation.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Young, KM (Dr Kaylene Young)
ID Code:73638
Year Published:2012 (online first 2011)
Web of Science® Times Cited:4
Deposited By:Menzies Institute for Medical Research
Deposited On:2011-10-19
Last Modified:2013-11-15
Downloads:0

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