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

56 Pages Posted: 18 Mar 2019 Sneak Peek Status: Review Complete

See all articles by Philip Dusart

Philip Dusart

Royal Institute of Technology (KTH) - Science for Life Laboratory

Björn M. Hallström

Royal Institute of Technology (KTH) - Science for Life Laboratory

Thomas Renne

University Medical Center Hamburg-Eppendorf - Institute for Clinical Chemistry and Laboratory Medicine

Jacob Odeberg

Royal Institute of Technology (KTH) - Science for Life Laboratory

Mathias Uhlen

Royal Institute of Technology (KTH) - Science for Life Laboratory

Lynn Butler

Royal Institute of Technology (KTH) - Science for Life Laboratory

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Abstract

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.

Keywords: Endothelium, RNAseq, Brain, Cortex, Cell identify, Glioblastoma Multiforme

Suggested Citation

Dusart, Philip and Hallström, Björn M. and Renne, Thomas and Odeberg, Jacob and Uhlen, Mathias and Butler, Lynn, A Systems-Based Map of Human Brain Cell-Type Enriched Genes and Malignancy-Associated Endothelial Changes (March 13, 2019). Available at SSRN: https://ssrn.com/abstract=3351829 or http://dx.doi.org/10.2139/ssrn.3351829
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Philip Dusart

Royal Institute of Technology (KTH) - Science for Life Laboratory

Stockholm, SE-100 44
Sweden

Björn M. Hallström

Royal Institute of Technology (KTH) - Science for Life Laboratory

Stockholm, SE-100 44
Sweden

Thomas Renne

University Medical Center Hamburg-Eppendorf - Institute for Clinical Chemistry and Laboratory Medicine

Martinistrasse 52
Hamburg, D - 20246
Germany

Jacob Odeberg

Royal Institute of Technology (KTH) - Science for Life Laboratory

Stockholm, SE-100 44
Sweden

Mathias Uhlen

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

Lynn Butler (Contact Author)

Royal Institute of Technology (KTH) - Science for Life Laboratory ( email )

Stockholm, SE-100 44
Sweden

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