Redox state is a central modulator of the balance between self-renewal anddifferentiation 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 different iation in dividing oligodendrocyte-type-2 astrocyte progenitor cells. The i ntracellular redox state of freshly isolated progenitors allows prospective isolation of cells with different self-renewal characteristics. Redox stat e is itself modulated by cell-extrinsic signaling molecules that alter the balance between self-renewal and differentiation: growth factors that promo te self-renewal cause progenitors to become more reduced, while signaling m olecules that promote differentiation cause progenitors to become more oxid ized. Moreover, pharmacological antagonists of the redox effects of these c ell-extrinsic signaling molecules antagonize their effects on self-renewal and differentiation, indicating that cell-extrinsic signaling molecules tha t modulate this balance converge on redox modulation as a critical componen t of their effector mechanism.