Document Type
Journal Article
Publication Date
12-19-2016
Journal
Nature Communications
Volume
7
DOI
10.1038/ncomms13866
Abstract
Regenerative processes in brain pathologies require the production of distinct neural cell populations from endogenous progenitor cells. We have previously demonstrated that oligodendrocyte progenitor cell (OPC) proliferation is crucial for oligodendrocyte (OL) regeneration in a mouse model of neonatal hypoxia (HX) that reproduces diffuse white matter injury (DWMI) of premature infants. Here we identify the histone deacetylase Sirt1 as a Cdk2 regulator in OPC proliferation and response to HX. HX enhances Sirt1 and Sirt1/Cdk2 complex formation through HIF1α activation. Sirt1 deacetylates retinoblastoma (Rb) in the Rb/E2F1 complex, leading to dissociation of E2F1 and enhanced OPC proliferation. Sirt1 knockdown in culture and its targeted ablation in vivo suppresses basal and HX-induced OPC proliferation. Inhibition of Sirt1 also promotes OPC differentiation after HX. Our results indicate that Sirt1 is an essential regulator of OPC proliferation and OL regeneration after neonatal brain injury. Therefore, enhancing Sirt1 activity may promote OL recovery after DWMI.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Jablonska, B., Gierdalski, M., Chew, L., Hawley, T., Catron, M., Lichauco, A., Cabrera-Luque, J., Yuen, T., Rowitch, D., & Gallo, V. (2016). Sirt1 regulates glial progenitor proliferation and regeneration in white matter after neonatal brain injury.. Nature Communications, 7 (). http://dx.doi.org/10.1038/ncomms13866
Peer Reviewed
1
Open Access
1
Comments
Reproduced with permission of Macmillan Publishers Ltd. Nature Communications