한빛사논문
- 조회261
Min Kyung Lee 1,*, Nasim Azizgolshani 1,2, Ze Zhang 1, Laurent Perreard 3, Fred W. Kolling 3, Lananh N. Nguyen 4, George J. Zanazzi 3,5, Lucas A. Salas 1 & Brock C. Christensen 1,6,7,*
1Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
2Department of Surgery, Columbia University Medical Center, New York, NY, USA.
3Dartmouth Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
4Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
5Department of Pathology and Laboratory Medicine, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
6Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
7Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
*Corresponding authors: correspondence to Min Kyung Lee or Brock C. Christensen
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.
논문정보
- Research article
- 2024년 04월 (BRIC 등록일 2024-05-07)
- 국외 연구진
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