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Cell autonomous regional differences in oligodendrocyte precursor cell development and response to oncohistone H3.3 K27M [ChIP-Seq]

GSE310474 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 40 samples Submitted 2026/05/22 Platform GPL24247
Summary
Diffuse midline glioma (DMG) is an incurable tumor arising in brainstem and midline structures. Most DMGs harbor missense histone H3 mutations replacing lysine 27 with methionine (H3 K27M). The mechanisms underlying regional selectivity for H3 K27M mutations, which are found almost exclusively in DMG, are not well understood. Here, we use a conditional knock-in mouse model to probe the postnatal brain region-specific oncogenic effects of H3.3 K27M in embryonic GFAP+ neural stem cells. We show that H3.3 K27M reduces oligodendrocyte differentiation in a region-specific manner and increases postnatal proliferation of distinct progenitor states by brain region in vivo, selectively expanding the oligodendrocyte-lineage in the ventral pons. Cellular morphology, marker expression, and transcriptomic analyses of primary region-specific mouse OPC cultures demonstrated cell-intrinsic differences in wild-type brainstem and forebrain OPC differentiation dynamics. H3.3 K27M drives cell-autonomous increase in brainstem-derived OPC proliferation and disrupts intrinsic region-specific transcriptional programs, delaying differentiation in forebrain-derived OPCs and restraining full maturation of brainstem-derived OPCs. H3.3 K27M-mediated changes include brainstem-selective upregulation of genes in Bmp, Wnt, and Notch pathways that are relevant in DMG pathogenesis. Our findings reveal that H3.3 K27M differentially disrupts cell-autonomous regional oligodendrocyte development, which may provide an opportunistic window for brainstem-selective gliomagenesis.
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Direct links to NCBI, no account and no request form: the whole study as GSE310474_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 40 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1366412 and SRA study SRP646867. Searching any of these in the dataset finder brings you back here.

Study design
40 conditions, each sampled once — no replicated groups

Read from 40 sample titles: 40 distinct titles with little repetition. Check it against the sample list below before relying on it.

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