HiTIP-seq profiles epigenomic reprogramming of patient-derived diffuse midline glioma stem cells to epigenetic therapy (IMAGE)
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Diffuse midline glioma (DMG), H3K27-altered, is a lethal pediatric high-grade tumor, lacking effective treatment options, primarily depending on clinical trials. Epigenetic agent-based immunotherapy has shown promise, but the underlying mechanisms remain unclear. To address the scarcity of tumor samples, researchers utilize patient-derived tumor cells to explore DMG heterogeneity. The epigenetic characteristics of DMG include a loss of H3K27me3 and a gain of H3K27ac. To overcome the limitations of traditional techniques, we developed high-throughput in situ tagged immunoprecipitation sequencing (HiTIP-seq) utilizing InSMART, enabling 100 parallel assays from just 100 cells on a single chip. Using this new method, we analyzed epigenetic alterations in 3D cell cultures derived from DMG patients, discovering that combinations of epigenetic agents (such as panobinostat and tazemetostat) can reprogram histone modifications and drive transcriptome changes, notably upregulating WIF1. HiTIP-seq provides a new tool for DMG research, showcasing hope in the fight against this deadly disease, and may ultimately lead to effective treatment options in the future.
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Peng Liu, School of Biomedical Engineering, Tsinghua University
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