AANS Online Scientific Sessions: Tumor-Reprogrammed TCA Cycle Maintains a Stem-Like Epitranscriptome and Therapeutic Persistence in Glioblastoma Stem Cells

Reprogrammed TCA Cycle Maintains a Stem-Like Epitranscriptome and Therapeutic Persistence in Glioblastoma Stem Cells

Video Transcription

Video Summary

In this video, Leo Kim, a sixth-year MSTP student at Case Western Reserve University, shares his research on glioblastoma stem cells (GSCs) in Dr. Jeremy Rich's lab at the Cleveland Clinic and UC San Diego. GSCs are characterized by their ability to self-renew, express stem cell markers, and differentiate into different lineages. The study investigated how GSCs alter their epigenetic plasticity as they differentiate. Using metabolite tracing experiments, they found that GSCs have a unique metabolic profile, specifically involving the malate-aspartate shuttle, which supports nucleotide biosynthesis. Knocking out or inhibiting malate dehydrogenase-2 (MbH2) in GSCs impaired their proliferation and sphere formation. The study also identified a therapeutic synergy between MbH2 inhibition and the drug satinib in GSCs. Overall, these findings provide insights into the metabolic and epigenetic regulation of GSCs.

Asset Subtitle

Leo Kim

Keywords

Leo Kim

glioblastoma stem cells

epigenetic plasticity

metabolic profile

malate dehydrogenase-2