Abstract Human glioblastoma (GBM) contains sharp spatial transitions in oxygen tension, metabolism, and lineage organization, yet how these microenvironmental cues become epigenetically encoded at the chromatin level remains poorly understood. Using cyclic immunofluorescence (CyCIF) on human IDH-wildtype GBM specimens enriched for necrosis, we mapped tumor cell lineages and histone H3K18 lactylation (H3K18la) at single-cell resolution. Necrotic and hypoxic regions displayed distinct lineage organization and elevated H3K18la, consistent with increased glycolytic flux and lactate accumulation under oxygen deprivation. In patient-derived GBM cell lines, hypoxia-mimetic treatment with deferoxamine (DFX) recapitulated this epigenetic response. RNA-sequencing and CUT Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 816.
Chakrabarty et al. (Fri,) studied this question.