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Single-cell lineage tracing of ispinesib-resistant glioma cells

ABSTRACT: To study the dynamics of GBM resistance and identify potential synergistic targets , we transfected PDGFR-amplified, patient-derived glioma neurospheres (TS543) with a barcoded lineage tracing library (CellTag), and treated the neurospheres with ispinesib. These genetically-modified, patient-derived neurospheres, which recapitulate key aspects of GBM heterogeneity, allow for surveillance of resistant phenotype on multiple timescales, and the barcode lineage tracing allows us to selectively analyze clones that are destined for resistance in the drug-naïve setting. We analyzed the phenotypes of the glioma cells during the long-term ispinesib treatment with single-cell RNAseq (scRNAseq), assess the stability and survival impact of drug-resistant phenotypes in the absence of drug and in orthotopic xenografts, and identified molecular markers of resistant clones in the drug-naïve setting to nominate effective drug combination.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE239651 | GEO | 2023/09/01

REPOSITORIES: GEO

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