Abstract
The subcortical white matter of the adult human brain harbors a pool of glial progenitor cells. These cells can be isolated by fluorescence-activated cell sorting (FACS) after either transfection with green fluorescent protein (GFP) under the control of the CNP2 promoter, or A2B5-targeted immunotagging. Although these cells give rise largely to oligodendrocytes, in low-density culture we observed that some also generated neurons. We thus asked whether these nominally glial progenitors might include multipotential progenitor cells capable of neurogenesis. We found that adult human white-matter progenitor cells (WMPCs) could be passaged as neurospheres in vitro and that these cells generated functionally competent neurons and glia both in vitro and after xenograft to the fetal rat brain. WMPCs were able to produce neurons after their initial isolation and did not require in vitro expansion or reprogramming to do so. These experiments indicate that an abundant pool of mitotically competent neurogenic progenitor cells resides in the adult human white matter.
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Acknowledgements
This study was supported by US National Institute of Neurological Disorders and Stroke grants R01NS39559, R01NS33106 and R37/R01NS29813, and by the National Multiple Sclerosis Society, Christopher Reeve Paralysis Foundation, and Project ALS. N.S.R. and M.N. were supported in part by the American Heart Association. M.N. was supported by the Fundação para a Ciencia e Tecnologia and the Gulbenkian Foundation of Portugal. We thank D. Trono for the lentiviral plasmids; C. Walsh for anti-doublecortin antisera; H. Furneaux for Hu-specific monoclonal antibody 16A11; R. Bansal and S. Pfeiffer for the monoclonal O4 line; and A. Benraiss, M. Windrem and T. Takano for advice and assistance.
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Nunes, M., Roy, N., Keyoung, H. et al. Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med 9, 439–447 (2003). https://doi.org/10.1038/nm837
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DOI: https://doi.org/10.1038/nm837
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