A Systems-Based Map of Human Brain Cell-Type Enriched Genes and Malignancy-Associated Endothelial Changes.

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Dusart P, Hallström BM, Renné T, Odeberg J, Uhlén M, Butler LM

Cell Reports 29 (6) 1690-1706.e4 [2019-11-05; online 2019-11-07]

Changes in the endothelium of the cerebral vasculature can contribute to inflammatory, thrombotic, and malignant disorders. The importance of defining cell-type-specific genes and their modification in disease is increasingly recognized. Here, we develop a bioinformatics-based approach to identify normal brain cell-enriched genes, using bulk RNA sequencing (RNA-seq) data from 238 normal human cortex samples from 2 independent cohorts. We compare endothelial cell-enriched gene profiles with astrocyte, oligodendrocyte, neuron, and microglial cell profiles. Endothelial changes in malignant disease are explored using RNA-seq data from 516 lower-grade gliomas and 401 glioblastomas. Lower-grade gliomas appear to be an "endothelial intermediate" between normal brain and glioblastoma. We apply our method for the prediction of glioblastoma-specific endothelial biomarkers, providing potential diagnostic or therapeutic targets. In summary, we provide a roadmap of endothelial cell identity in normal and malignant brain, using a method developed to resolve bulk RNA-seq into constituent cell-type-enriched profiles.

PubMed 31693905

DOI 10.1016/j.celrep.2019.09.088

Crossref 10.1016/j.celrep.2019.09.088

pii: S2211-1247(19)31292-6