Redox state is a central modulator of the balance between self-renewal and differentiation in a dividing glial precursor cell.
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.
Smith
J
J
Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, 2000 N. Medical Drive, Room 4280, Salt Lake City, UT 84112, USA.
Ladi
E
E
Mayer-Proschel
M
M
Noble
M
M
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D006706:Homeostasis; D009457:Neuroglia / Q000166:cytology* / Q000502:physiology*; D009900:Optic Nerve / Q000166:cytology / Q000502:physiology; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D000975:Antioxidants; D016877:Oxidants; D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D019328:Buthionine Sulfoximine; D020122:tert-Butylhydroperoxide; D000111:Acetylcysteine