Figure 2.

Sirt2i reverts Atrx-deficient transcriptional profiles, impacting motility and senescence. (A) GSEA plots documenting reversion of Atrx-deficient transcriptional signatures upon Sirt2i (AGK2: 1uM, AK7 and Thiomyristoyl: 10 µM) in Atrx− mNPCs. Dotted lines indicate the positioning of 0.0 enrichment scores. (B) Schematic of significantly enriched, negatively correlated GSEA pathways noted upon Sirt2i in Atrx- mNPCs. (C) 24-hour transwell migration assays for Atrx + and Atrx- mNPCs treated with Sirt2i (AGK2: 1 µM, AK7 and Thiomyristoyl: 10 µM) or vehicle control. (D) Quantified β-Galactosidase staining data for mNPCs (left) and GSCs (middle: TS603 and GS5-22, and right:TS543 and TS543 shATRX) demonstrating increased senescence with Sirt2i (AGK2: 1 µM, AK7 and Thiomyristoyl: 10 µM) in Atrx/ATRX-deficient contexts. (E) Heatmap showing expression levels of SenMayo database genes in Atrx− mNPCs treated with either DMSO or Sirt2i (AGK2: 1 µM, AK7 and Thiomyristoyl: 10 µM). (F) RT-PCR for senescence-associated transcripts ETS2 and SEMA3F showing larger increases upon 1uM AGK2 treatment in ATRX-mutant GSCs (GS 5-22) than in ATRX-wildtype GSCs (TS 603). Where applicable, error bars reflect SEM; p values determined by unpaired, two-tailed t-test. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001