GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE344nnn/GSE344027/primary200OKGenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE344027GEOGSEfalseAutophagy Inhibition Sensitizes Radiotherapy Responses in High-grade Mutant IDH1 Glioma [CUT&Run]Mutant isocitrate dehydrogenase 1 (mIDH1) catalyzes 2-hydroxyglutarate (2-HG) production which leads to epigenetic reprogramming in astrocytomas with TP53/ATRX loss. RNA-sequencing, single-cell RNA-sequencing, and Chromatin Immunoprecipitation sequencing followed by analysis shows that human and mouse mIDH1 gliomas exhibit downregulated gene ontologies (GOs) related to mitochondrial metabolism and upregulated autophagy-related GOs. Decreased mitochondrial metabolism is accompanied by decreased glycolysis, rendering autophagy as a source of energy in mIDH1 gliomas. Mutant IDH1 glioma cells exhibit increased expression of autophagy-related proteins and enhanced LC3 I/II conversion, indicating augmented autophagy. Inhibiting autophagy in vivo by administration of synthetic protein nanoparticles encapsulating autophagy related gene 7 silencing RNA sensitized mIDH1 glioma cells to radiation, resulting in tumor regression, long-term survival, and immunological memory. This work uncovers autophagy as a critical pathway for survival in mIDH1 gliomas and its inhibition elicits radiosensitivity in vitro in human and mouse mIDH1 glioma cells, and in vivo in mIDH1 models.2026/08/17GSE344027GSM9966573GSM9966568GSM9966571GSM996657034475344027Mus musculus[42760279]