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Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10032-7.

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

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Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, 2000 N. Medical Drive, Room 4280, Salt Lake City, UT 84112, USA.


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.

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