한빛사논문
Min Kyung Lee 1, Nasim Azizgolshani 1,2, Joshua A. Shapiro 3, Lananh N. Nguyen 4, Fred W. Kolling 5, George J. Zanazzi 5,6, Hildreth Robert Frost 7 & Brock C. Christensen 1,8,9,*
1Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
2Department of Surgery, Columbia University Irving Medical Center, New York, NY, USA.
3Childhood Cancer Data Lab, Alex’s Lemonade Stand Foundation, Bala Cynwyd, PA, USA.
4Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
5Dartmouth Cancer Center, Lebanon, NH, USA.
6Department of Pathology and Laboratory Medicine, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
7Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
8Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
9Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
*Corresponding author: correspondence to Brock C. Christensen
Abstract
Central nervous system (CNS) tumors are the leading cause of pediatric cancer death, and these patients have an increased risk for developing secondary neoplasms. Due to the low prevalence of pediatric CNS tumors, major advances in targeted therapies have been lagging compared to other adult tumors. We collect single nuclei RNA-seq data from 84,700 nuclei of 35 pediatric CNS tumors and three non-tumoral pediatric brain tissues and characterize tumor heterogeneity and transcriptomic alterations. We distinguish cell subpopulations associated with specific tumor types including radial glial cells in ependymomas and oligodendrocyte precursor cells in astrocytomas. In tumors, we observe pathways important in neural stem cell-like populations, a cell type previously associated with therapy resistance. Lastly, we identify transcriptomic alterations among pediatric CNS tumor types compared to non-tumor tissues, while accounting for cell type effects on gene expression. Our results suggest potential tumor type and cell type-specific targets for pediatric CNS tumor treatment. Here we address current gaps in understanding single nuclei gene expression profiles of previously under-investigated tumor types and enhance current knowledge of gene expression profiles of single cells of various pediatric CNS tumors.
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