SCIENCE SIGNALING

Sirtuin to Become Astrocytes

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Science  18 Apr 2008:
Vol. 320, Issue 5874, pp. 291
DOI: 10.1126/science.320.5874.291c

Although neural progenitor cells (NPCs) can differentiate into neurons, astrocytes, or oligodendrocytes, brain injury stimulates the production of astrocytes in preference to neurons. Noting that some neurological diseases are associated with inflammation and oxidative conditions, Prozorovski et al. investigated the effects of redox state on NPC differentiation. The fraction of cultured NPCs that differentiated into astrocytes was larger under oxidative conditions, whereas the fraction that differentiated into neurons was smaller. Conversely, NPCs cultured under reducing conditions were more likely to differentiate into neurons and less likely to differentiate into astrocytes. The amount of the histone deacetylase Sirtuin1 (Sirt1) was increased in NPCs cultured under oxidative conditions, and Sirt1 knockdown blocked the effects of oxidation on differentiation. Oxidative conditions promoted the association of Sirt1 with the transcription factor Hes1 and decreased the expression of Mash1, which encodes a neurogenic transcription factor. Mouse pups injected with a pro-oxidant showed an increase in Sirt1 in a germinal region of the brain, along with a decrease in neurogenesis; in utero knockdown of Sirt1 increased neurogenesis in such oxidant-treated pups. Thus, the authors conclude that nontoxic manipulation of redox conditions can influence NPC fate, and that Sirt1 plays a critical role. — EMA

Nat. Cell Biol. 10, 385 (2008).

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