Fig. 3: Isogenic NSC models driven by FGFR1 alterations grow and signal independently of growth factor. | Nature Communications

Fig. 3: Isogenic NSC models driven by FGFR1 alterations grow and signal independently of growth factor.

From: A diverse landscape of FGFR alterations and co-mutations suggests potential therapeutic strategies in pediatric low-grade gliomas

Fig. 3

a Overview of the generation of the isogenic NSC lines. Mouse or hTERT-immortalized human NSCs were virally transduced with each of the FGFR or BRAF alterations, or control vectors, followed by a second transduction containing the co-occurring PTPN11 mutation or control vectors. Created in BioRender. Apfelbaum, A. (2024) https://BioRender.com/p48w741. b Bar plots depicting the percentage of cumulative doubling growth rate at day 14 for each mNSC cell line grown with no growth factor (no gf)/with growth factor (+gf). Values and error bars depict the mean ± SEM of three independent biological replicates. Significance calculated by a Welch’s two-sided t test compared to the vehicle control. *p < 0.05, **p < 0.01, ***p < 0.001. c Same as in b but for the ihNSC lines. Representative immunoblots (densitometry of three biological replicates in Supplementary Fig. S5j–o) of downstream MAPK and PI3K/mTOR signaling pathway effectors for d mNSC and e ihNSC models. Phosphorylated proteins represent activated signaling pathways. pERK is a readout for MAPK signaling, and pAKT and pS6 are readouts for PI3K/mTOR signaling. Vector Control and PTPN11 alone are grown in the presence of growth factor, while lines harboring FGFR1 and BRAF drivers are grown without growth factor supplementation. Abbreviations for models= F1-N546K: FGFR1 N546K SNV, F1-N546K + PTPN11: FGFR1 N546K SNV + PTPN11 E69K SNV, F1-ITD: FGFR1-ITD, F1::TACC1: FGFR1::TACC1, V600E: BRAF V600E SNV, K::B: KIAA1549::BRAF. Source data provided in the Source Data File.

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