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Fate determination of adult human glial progenitor cells

Published online by Cambridge University Press:  07 October 2009

Fraser J. Sim ,
Martha S. Windrem  and
Steven A. Goldman
Fraser J. Sim
Affiliation:
Center for Translational Neuromedicine, and the Department of Neurology, University of Rochester Medical Center, Rochester, NY
Martha S. Windrem
Affiliation:
Center for Translational Neuromedicine, and the Department of Neurology, University of Rochester Medical Center, Rochester, NY
Steven A. Goldman*
Affiliation:
Center for Translational Neuromedicine, and the Department of Neurology, University of Rochester Medical Center, Rochester, NY
*
Correspondence should be addressed to: Steven A. Goldman, Department of Neurology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 645, Rochester, NY, USA phone: 14642 585-275-9588 email: Steven_Goldman@urmc.rochester.edu
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Abstract

Glial progenitor cells (GPCs) comprise the most abundant population of progenitor cells in the adult human brain. They are responsible for central nervous system (CNS) remyelination, and likely contribute to the astrogliotic response to brain injury and degeneration as well. Adult human GPCs are biased to differentiate as oligodendrocytes and elaborate new myelin, and yet they retain multilineage plasticity, and can give rise to neurons as well as astrocytes and oligodendrocytes once removed from the adult parenchymal environment. GPCs retain strong mechanisms for cell-autonomous self-renewal, and yet both their phenotype and fate may be dictated by their microenvironment. Using the transcriptional profiles of acutely isolated GPCs, we have begun to understand the operative ligand–receptor interactions involved in these processes, and have identified several key signaling pathways by which adult human GPCs may be reliably instructed to either oligodendrocytic or astrocytic fate. In addition, we have noted significant differences between the expressed genes and dominant signaling pathways of fetal and adult human GPCs, as well as between rodent and human GPCs. The latter data in particular call into question therapeutic strategies predicated solely upon data obtained using rodents, while perhaps highlighting the extent to which evolution has been attended by the phylogenetic modification of glial phenotype and function.

Keywords

Oligodendrocytesgenomicsprogenitor cellsstem cellsmyelination
Type
Research Article
Information
Neuron Glia Biology , Volume 5 , Special Issue 3-4: NG2-Glia, Part II: NG2 Cells as Neural Precursors , November 2009 , pp. 45 - 55
Copyright
Copyright © Cambridge University Press 2009

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