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PNAS 97 (18): 10032-10037

Copyright © 2000 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / DEVELOPMENTAL BIOLOGY

Redox state is a central modulator of the balance between self-renewal and differentiation in a dividing glial precursor cell

Joel Smith*, Ena Ladi{dagger}, Margot Mayer-Pröschel{ddagger}, and Mark Noble{ddagger},§

*Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, 2000 N. Medical Drive, Room 4280, Salt Lake City, UT 84112; {dagger}Department of Biological Chemistry, UCLA School of Medicine, Los Angeles, CA 90095; and {ddagger}Center for Cancer Biology, AAB Institute for Biomedical Sciences, Box 633, University of Rochester, 601 Elmwood Ave, Rochester, NY 14610

Received for publication May 9, 2000.

Abstract: We have discovered that intracellular redox state appears to be a necessary and sufficient modulator of the balance between self-renewal and differentiation in dividing oligodendrocyte-type-2 astrocyte progenitor cells. The intracellular redox state of freshly isolated progenitors allows prospective isolation of cells with different self-renewal characteristics. Redox state is itself modulated by cell-extrinsic signaling molecules that alter the balance between self-renewal and differentiation: growth factors that promote self-renewal cause progenitors to become more reduced, while signaling molecules that promote differentiation cause progenitors to become more oxidized. Moreover, pharmacological antagonists of the redox effects of these cell-extrinsic signaling molecules antagonize their effects on self-renewal and differentiation, indicating that cell-extrinsic signaling molecules that modulate this balance converge on redox modulation as a critical component of their effector mechanism.

§ To whom all reprint requests should be addressed. E-mail: mark_noble{at}urmc.rochester.edu.

Edited by Darwin J. Prockop, MCP Hahnemann University, Philadelphia, PA, and approved June 14, 2000

This paper was submitted directly (Track II) to the PNAS office.

Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.170209797.

Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.170209797

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