Fig. 3: Silencing TERT expression or the ALT pathway normalizes 1H-MRS biomarkers and hyperpolarized [1-13C]-alanine metabolism in patient-derived LGOG and LGA models.
From: Non-invasive assessment of telomere maintenance mechanisms in brain tumors
a Effect of TERT silencing on steady-state metabolite levels as measured by 1H-MRS in the BT54 LGOG model (BT54 TERT + neurospheres: red circles; BT54 TERT− #1 neurospheres: dark brown circles; BT54 TERT− #2 neurospheres: light brown circles). TERT silencing was carried out with two independent, nonoverlapping siRNA sequences/pools. b Representative summed 13C-MRS spectra showing hyperpolarized [1-13C]-alanine metabolism in BT54 TERT+ and BT54 TERT− neurospheres. c Quantification of the ratios for hyperpolarized lactate/alanine and hyperpolarized pyruvate/alanine in BT54 TERT+ and TERT− neurospheres (BT54 TERT+ neurospheres: red circles; BT54 TERT− #1 neurospheres: dark brown circles; BT54 TERT− #2 neurospheres: light brown circles). TERT silencing was carried out with two independent, nonoverlapping siRNA sequences/pools. d Effect of silencing the ALT pathway via ATRX re-expression on steady-state metabolite levels as measured by 1H-MRS in the BT142 LGA model (BT142 ALT+ neurospheres: magenta circles; BT142 ALT− neurospheres (lavender circles). e Representative summed 13C-MRS spectra showing hyperpolarized [1-13C]-alanine metabolism in BT142 ALT+ and BT142 ALT− neurospheres. f Quantification of the ratios for hyperpolarized pyruvate/alanine and hyperpolarized lactate/alanine in BT142 ALT+ (magenta circles) and BT142 ALT− (lavender circles) neurospheres. All experiments were performed on three biological replicates (n = 3). Results are presented as mean ± standard deviation. Statistical significance was assessed using an unpaired Student’s t test assuming unequal variance with p < 0.05 considered significant. Correction for multiple comparisons was performed using the Holm–ŠÃdák method. *** represents statistical significance with p < 0.005; ** represents statistical significance with p < 0.01; * represents statistical significance with p < 0.05. Also, refer to Supplementary Fig. 4. Source data with exact p values are provided as a source data file.
