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Next Article 
Journal of Neuroscience, Vol 14, 4571-4587, Copyright © 1994 by Society for Neuroscience
Plasticity in the adult human oligodendrocyte lineage
N Gogate, L Verma, JM Zhou, E Milward, R Rusten, M O'Connor, C Kufta, J Kim, L Hudson and M Dubois-Dalcq
Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Preoligodendrocytes have been described in cultures and tissue prints of
adult human white matter (Armstrong et al., 1992). To characterize further
these precursors of human oligodendrocytes, we have investigated whether
they express genes playing a critical role in oligodendrocyte development.
In the intact human brain, platelet- derived growth factor receptor alpha
(PDGF alpha R) and myelin transcription factor 1 (MyTI) transcripts are
expressed in 1-2% of cells of the oligodendrocyte lineage (OL), and
clusters of such cells can be found in the periventricular region. Myelin
basic protein transcripts containing exon 2 information (exon 2+ MBP),
which are characteristic of the premyelinating stage, are detected in
15-20% of OL cells in vivo. When OL cells are separated from human white
matter and allowed to regenerate in vitro, a much larger proportion of
these cells express developmentally regulated genes, while exon 2- MBP and
proteolipid protein (PLP) transcripts characteristic of mature OL cells
appear transiently downregulated. Basic fibroblast growth factor (bFGF),
even in the presence of PDGF, does not promote DNA synthesis in these
cultured OL cells. Yet bFGF induces human oligodendrocytes to regenerate
their processes rapidly in vitro and to express O4 antigens as well as exon
2+ MBP, MyTI, and PLP transcripts. While bFGF accelerates early
regenerative processes, it also maintains high expression of exon 2+ MBP
transcripts in OL cells for up to 2 weeks in vitro. In contrast, high
levels of insulin in the absence of bFGF allow accumulation of exon 2- MBP
and PLP transcripts in most OL cells at 2-3 weeks in vitro. We propose that
the myelinated human brain harbors a small pool of precursors of
oligodendrocytes and that growth factor- regulated phenotypic plasticity
rather than mitogenic potential accounts for the regeneration of
oligodendrocytes in the initial stages of demyelinating diseases such as
multiple sclerosis.
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