RT Journal Article SR Electronic T1 A systems-based map of human brain cell-type enriched genes and malignancy-associated endothelial changes JF bioRxiv FD Cold Spring Harbor Laboratory SP 528414 DO 10.1101/528414 A1 Philip Dusart A1 Björn M Hallström A1 Thomas Renne A1 Jacob Odeberg A1 Mathias Uhlén A1 Lynn M Butler YR 2019 UL http://biorxiv.org/content/early/2019/02/05/528414.abstract AB 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 how they are modified in disease is increasingly recognised. Here, we developed a bioinformatics-based approach to identify normal brain cell-enriched genes, using bulk RNAseq data from 238 normal human cortex samples from 2 independent cohorts. We compared endothelial cell-enriched gene profiles with astrocyte, oligodendrocyte and neuron profiles. Global modifications to the endothelium in malignant disease were characterised, using RNAseq data from 516 human lower grade gliomas and 401 human glioblastoma multiforme samples. Lower grade glioma appeared to be an ‘endothelial intermediate’ between normal brain and glioblastoma multiforme. We identify the most highly glioblastoma multiforme-specific endothelial cell biomarkers, providing potential diagnostic or therapeutic targets. In summary, we provide a roadmap of endothelial cell identity in normal and malignant brain tissue, using a bioinformatics-based method developed to resolve bulk RNAseq datasets into constituent cell type-enriched profiles.