Associations in cell type-specific hydroxymethylation and transcriptional alterations of pediatric central nervous system tumors

Min Kyung Lee (), Nasim Azizgolshani, Ze Zhang, Laurent Perreard, Fred W. Kolling, Lananh N. Nguyen, George J. Zanazzi, Lucas A. Salas and Brock C. Christensen ()
Additional contact information
Min Kyung Lee: Geisel School of Medicine at Dartmouth
Nasim Azizgolshani: Geisel School of Medicine at Dartmouth
Ze Zhang: Geisel School of Medicine at Dartmouth
Laurent Perreard: Geisel School of Medicine at Dartmouth
Fred W. Kolling: Geisel School of Medicine at Dartmouth
Lananh N. Nguyen: University of Toronto
George J. Zanazzi: Geisel School of Medicine at Dartmouth
Lucas A. Salas: Geisel School of Medicine at Dartmouth
Brock C. Christensen: Geisel School of Medicine at Dartmouth

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Although intratumoral heterogeneity has been established in pediatric central nervous system tumors, epigenomic alterations at the cell type level have largely remained unresolved. To identify cell type-specific alterations to cytosine modifications in pediatric central nervous system tumors, we utilize a multi-omic approach that integrated bulk DNA cytosine modification data (methylation and hydroxymethylation) with both bulk and single-cell RNA-sequencing data. We demonstrate a large reduction in the scope of significantly differentially modified cytosines in tumors when accounting for tumor cell type composition. In the progenitor-like cell types of tumors, we identify a preponderance differential Cytosine-phosphate-Guanine site hydroxymethylation rather than methylation. Genes with differential hydroxymethylation, like histone deacetylase 4 and insulin-like growth factor 1 receptor, are associated with cell type-specific changes in gene expression in tumors. Our results highlight the importance of epigenomic alterations in the progenitor-like cell types and its role in cell type-specific transcriptional regulation in pediatric central nervous system tumors.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-47943-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47943-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-47943-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().