OSCR

Cell autonomous regional differences in oligodendrocyte lineage development and responses to oncohistone H3.3 K27M.

Overview

Authors: Jared M Andrews1,2, Kaitlin M Budd1,2,3, Chang-Hyuk Kwon1,2, Jon D Larson1, Abbas Shirinifard1, Lawryn H Kasper1,2, Chanrika C Williams1,2, Alfonso Lavado4,5, Sharon King1, Jorge Gutierrez6, Daniel Stabley1, Tong Lin7, Sara A Lewis1,2, Paul A Northcott1,2, Arzu Onar-Thomas7, Suzanne J Baker1,2
ORCID iDs: Jared M Andrews, Kaitlin M Budd, Sharon King, Sara A Lewis, Paul A Northcott, Suzanne J Baker
  1. Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN USA
  2. Center of Excellence in Neuro-Oncology Sciences, St. Jude Children’s Research Hospital, Memphis, TN USA
  3. St. Jude Graduate School of Biomedical Sciences, St. Jude Children’s Research Hospital, Memphis, TN USA
  4. Center for Pediatric Neurological Disease Research, St. Jude Children’s Research Hospital, Memphis, TN USA
  5. Department of Cell and Molecular Biology, St. Jude Children’s Research Hospital, Memphis, TN USA
  6. Information Services, St. Jude Children’s Research Hospital, Memphis, TN USA
  7. Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN USA
Institutions: St. Jude Children's Research Hospital (United States)
Journal: Nature communications, volume 17, issue 1, article 8811
Dates: received 3 March 2025; accepted 30 July 2026; published online 26 August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-76468-6 · PMID 42649219 · PMCID PMC13518833 · OpenAlex W7204231809
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), other condition (population), cellular / molecular (subfield)
Methods: Spectral & time-frequency, Statistics, Smoothing, state filtering, decompositions, Machine learning, Evoked potentials, Connectivity, fMRI & imaging, Physiology & signal measures
Keywords: Differentiation, CNS cancer, Paediatric cancer, Glial biology, Epigenetic memory
MeSH: Brain Neoplasms*, Glioma*, Histones*, Oligodendroglia*, Animals, Cell Differentiation, Cell Lineage, Cell Proliferation, Gene Knock-In Techniques, Mice, Mutation, Oligodendrocyte Precursor Cells (* major topic)
Topic: Glioma Diagnosis and Treatment (Genetics, Medicine), according to OpenAlex
Funding: NCI NIH HHS (F31 CA265285, P01 CA096832, P30 CA021765); U.S. Department of Health & Human Services | NIH | National Cancer Institute (F31CA265285); U.S. Department of Health & Human Services | National Institutes of Health (P30CA021765, F31CA265285, P01CA096832); St. Jude Children's Research Hospital (The Transcription Collaborative); St. Jude Children's Research Hospital (The Transcription Collaborative); American Lebanese Syrian Associated Charities
Citations: not cited yet (Europe PMC); 99 references in the paper

Abstract

Diffuse midline glioma, H3K27-altered (DMG), is a lethal midline brain tumor. Most DMG, unlike glioma arising in other regions, harbor histone H3.3 K27M (K27M) mutations. The basis for this anatomical selectivity remains unclear. Stem-like DMG cell transcriptomes most resemble oligodendrocyte precursor cells (OPCs). Using conditional K27M knock-in mice, we show that K27M reduces oligodendrocyte differentiation, altering the proportions of oligodendrocytic cell states in a region-specific manner. In vivo EdU labeling in tissue-cleared whole brains revealed greater K27M-driven increases in proliferation within pons, midline, and hindbrain regions than in telencephalon. In vitro, wild-type brainstem OPCs proliferate more slowly and differentiate later than telencephalic OPCs. K27M enhances brainstem OPC proliferation and disrupts regional transcriptional programs, selectively restraining full maturation of brainstem OPCs while inducing brainstem-selective upregulation of bivalent Bmp, Wnt, and Notch pathway genes. These findings suggest that K27M exploits intrinsic regional differences in oligodendrocyte development, creating a brainstem-selective window for gliomagenesis.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

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Data

Datasets cited

Data availability

All sequencing data generated for this project were deposited at GEO under accessions GSE290816 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290816), GSE290817 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290817), GSE310474 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310474), and GSE310472 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310472). H3 K27M DMG xenograft data used from24 are available at GEO under accession GSE115875 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE115875). Primary human DMG data used from43 is available at EGA under accession EGAS00001000192 (https://ega-archive.org/studies/EGAS00001000192). K27M-flag, WT-flag, and K27M mice without a tag are available upon request to the Baker lab. Due to the large size of cleared whole-brain imaging files (>250 GB per sample), full regional quantifications are provided as supplemental and source data, with full imaging datasets available on request. Source data are provided with this paper and on figshare at 10.6084/m9.figshare.31004440.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 16 authors, 5 keywords, 12 MeSH terms, 6 funders, 97 references.

Cite

This paper

Andrews, J. M., Budd, K. M., Kwon, C.-H., Larson, J. D., Shirinifard, A., Kasper, L. H., Williams, C. C., Lavado, A., King, S., Gutierrez, J., Stabley, D., Lin, T., Lewis, S. A., Northcott, P. A., Onar-Thomas, A., & Baker, S. J. (2026). Cell autonomous regional differences in oligodendrocyte lineage development and responses to oncohistone H3.3 K27M. Nature communications, 17(1), 8811. https://doi.org/10.1038/s41467-026-76468-6

BibTeX

@article{andrews2026cell,
author = {Andrews, Jared M and Budd, Kaitlin M and Kwon, Chang-Hyuk and Larson, Jon D and Shirinifard, Abbas and Kasper, Lawryn H and Williams, Chanrika C and Lavado, Alfonso and King, Sharon and Gutierrez, Jorge and Stabley, Daniel and Lin, Tong and Lewis, Sara A and Northcott, Paul A and Onar-Thomas, Arzu and Baker, Suzanne J},
title = {{Cell autonomous regional differences in oligodendrocyte lineage development and responses to oncohistone H3.3 K27M}},
journal = {Nature communications},
year = {2026},
month = aug,
volume = {17},
number = {1},
pages = {8811},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-76468-6},
url = {https://doi.org/10.1038/s41467-026-76468-6},
pmid = {42649219},
pmcid = {PMC13518833}
}

RIS

TY - JOUR
AU - Andrews, Jared M
AU - Budd, Kaitlin M
AU - Kwon, Chang-Hyuk
AU - Larson, Jon D
AU - Shirinifard, Abbas
AU - Kasper, Lawryn H
AU - Williams, Chanrika C
AU - Lavado, Alfonso
AU - King, Sharon
AU - Gutierrez, Jorge
AU - Stabley, Daniel
AU - Lin, Tong
AU - Lewis, Sara A
AU - Northcott, Paul A
AU - Onar-Thomas, Arzu
AU - Baker, Suzanne J
TI - Cell autonomous regional differences in oligodendrocyte lineage development and responses to oncohistone H3.3 K27M
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/08/26
VL - 17
IS - 1
SP - 8811
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-76468-6
UR - https://doi.org/10.1038/s41467-026-76468-6
LA - en
ER -

CSL-JSON

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