EPCO-13. IDENTIFYING REGULATORS OF GLIOMA CELL STATE DIVERSITY AND EVOLUTION VIA JOINT SINGLE NUCLEUS RNA AND CHROMATIN ACCESSIBILITY

Abstract Glioma cellular heterogeneity and plasticity represent fundamental obstacles to effective therapies. Understanding the determinants that govern glioma cell diversity adaptability is critical overcoming treatment resistance. Recent single DNA methylation studies have demonstrated dynamic epigenetic alterations facilitate state shifts stress response. However, information regarding other modes of gene regulation, such as chromatin accessibility, how therapy shapes remains limited. To determine regulators under treatment, we profiled 36 tumors (n = 23 adult patients) with joint nucleus RNA ATACseq including 13 longitudinal initial – recurrent pairs yielded a total 79,945 cells (37,883 malignant cells). We identified peaks were uniquely open in 14,462 peaks, FDR < 0.05) compared tumor microenvironmental neuronal, perivascular, glial, immune populations. Among cells, differentiated-like exhibited more regions accessibility than stem-like cells. These populations could be further delineated by differential peak enrichment transcription factor binding sites (TCF12, ASCL1), (SMARCC1, JUN), proliferating (E2F4) nominating these factors master regulators. confirmed state-specific overlapped enhancer via multiomics bulk H3K27ac profiling 3 patient-derived lines. there are changes at recurrence trend toward was associated coordinated transcriptional changes. Finally, incorporated matched whole genome sequencing data evaluate mutational profiles differentiate between predominantly epigenetically driven epigenomic co-evolution genome. Together, findings define key switches shape states during progression.