Single-nucleus RNA-seq dissection of choroid plexus tumor cell heterogeneity

EMBO J. 2024 Oct 31. doi: 10.1038/s44318-024-00283-2. Online ahead of print.

Abstract

The genomic, genetic and cellular events regulating the onset, growth and survival of rare, choroid plexus neoplasms remain poorly understood. Here, we examine the heterogeneity of human choroid plexus tumors by single-nucleus transcriptome analysis of 23,906 cells from four disease-free choroid plexus and eleven choroid plexus tumors. The resulting expression atlas profiles cellular and transcriptional diversity, copy number alterations, and cell-cell interaction networks in normal and cancerous choroid plexus. In choroid plexus tumor epithelial cells, we observe transcriptional changes that correlate with genome-wide methylation profiles. We further characterize tumor type-specific stromal microenvironments that include altered macrophage and mesenchymal cell states, as well as changes in extracellular matrix components. This first single-cell dataset resource from such scarce samples should be valuable for divising therapies against these little-studied neoplasms.

Keywords: Cerebrospinal Fluid (CSF); Choroid Plexus Tumors; Single Cell RNAseq; Tumor Microenvironment.