Figure 2.

Inducible inactivation of SIRT1 in adult NSCs and neural progenitors expands the oligodendrocyte lineage. (a) SIRT1 can be conditionally inactivated in adult NSCs and neural progenitors by tamoxifen injection of NestinCreER;mT/mG;Sirt1^lox/lox mice. Upper left: schematic of a coronal mouse brain section. LV, lateral ventricle; SVZ, subventricular zone; Sep, septum; Str, striatum; CC, corpus callosum. Not drawn to scale. Upper right, adult mice were injected with tamoxifen once before analysis. Bottom, membrane-targeted green fluorescent protein (mGFP) serves as a reporter for Cre recombinase activity in NestinCreER;mT/mG;Sirt1^lox/lox mice. (b) Progeny of adult NSCs and neural progenitors were observed in the striatum and septum of both NestinCreER;mT/mG;Sirt1^lox/lox and NestinCreER;mT/mG control mice 10 days after tamoxifen injection. Concentrated areas of membrane-targeted tomato red fluorescent protein (mTFP) are blood vessels. (c) Inactivation of SIRT1 in adult NSCs and neural progenitors leads to greater production of OLIG2-positive NSC and neural progenitor progeny in the surrounding NSC niche. Mean±s.e.m. of 4 independent cohorts of 2 mice per genotype for each cohort, except one in which there were 3 control mice (n = 4). Two-tailed, paired Student’s t-test, striatum, *P =0.0294; septum, *P =0.0174. Arrowheads point to cells co-expressing mGFP and OLIG2. (d) mGFP-positive cells with morphologies characteristic of myelinating oligodendrocytes were observed in the striatum and septum of NestinCreER;mT/mG;Sirt1^lox/lox brains. (e) Deletion of active SIRT1 in adult NSCs and neural progenitors leads to greater production of GFAP-positive NSC and neural progenitor progeny in the surrounding NSC niche. Mean±s.e.m. of 4 independent cohorts of 2 mice per genotype for each cohort, except one in which there were 3 control mice (n = 4). Two-tailed, paired Student’s t-test, striatum, *P = 0.0282; septum, *P = 0.0144. Arrowheads point to cells co-expressing mGFP and GFAP. (f) Deletion of active SIRT1 in adult NSCs and neural progenitors enhances the area in the olfactory bulb (OB) covered by mGFP fluorescence 10 days after tamoxifen injection. Mean±s.e.m. of n = 3 NestinCreER;mT/mG and n = 4 NestinCreER;mT/mG;Sirt1^lox/lox mice. Two-tailed, unpaired Student’s t-test, *P = 0.01. Tam, tamoxifen. All scale bars, 50 μm.