Language
English
Publication Date
12-1-2022
Journal
Nature Genetics
DOI
10.1038/s41588-022-01205-w
PMID
36471070
PMCID
PMC9742294
PubMedCentral® Posted Date
6-5-2023
PubMedCentral® Full Text Version
Author MSS
Abstract
Canonical (H3.1/H3.2) and noncanonical (H3.3) histone 3 K27M-mutant gliomas have unique spatiotemporal distributions, partner alterations and molecular profiles. The contribution of the cell of origin to these differences has been challenging to uncouple from the oncogenic reprogramming induced by the mutation. Here, we perform an integrated analysis of 116 tumors, including single-cell transcriptome and chromatin accessibility, 3D chromatin architecture and epigenomic profiles, and show that K27M-mutant gliomas faithfully maintain chromatin configuration at developmental genes consistent with anatomically distinct oligodendrocyte precursor cells (OPCs). H3.3K27M thalamic gliomas map to prosomere 2-derived lineages. In turn, H3.1K27M ACVR1-mutant pontine gliomas uniformly mirror early ventral NKX6-1
Keywords
Cell Lineage, Epigenomics, Chromatin, Brain, K27M, EZHIP, OPC, oligodendrocyte development, ACVR1, single cell multiomics, Nkx6-1, Pax3, BMP
Published Open-Access
yes
Recommended Citation
Jessa, Selin; Mohammadnia, Abdulshakour; Harutyunyan, Ashot S; et al., "K27M in Canonical and Noncanonical H3 Variants Occurs in Distinct Oligodendroglial Cell Lineages in Brain Midline Gliomas" (2022). Faculty and Staff Publications. 5387.
https://digitalcommons.library.tmc.edu/baylor_docs/5387