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

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A Systems-Based Map of Human Brain Cell-Type Enriched Genes and Malignancy-Associated Endothelial Changes. / Dusart, Philip; Hallström, Björn Mikael; Renné, Thomas; Odeberg, Jacob; Uhlén, Mathias; Butler, Lynn Marie.

In: CELL REP, Vol. 29, No. 6, 05.11.2019, p. 1690-1706.e4.

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@article{9441fc96d1e9401cbafed6e76e262711,
title = "A Systems-Based Map of Human Brain Cell-Type Enriched Genes and Malignancy-Associated Endothelial Changes",
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 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.",
author = "Philip Dusart and Hallstr{\"o}m, {Bj{\"o}rn Mikael} and Thomas Renn{\'e} and Jacob Odeberg and Mathias Uhl{\'e}n and Butler, {Lynn Marie}",
note = "Copyright {\textcopyright} 2019 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2019",
month = nov,
day = "5",
doi = "10.1016/j.celrep.2019.09.088",
language = "English",
volume = "29",
pages = "1690--1706.e4",
journal = "CELL REP",
issn = "2211-1247",
publisher = "Elsevier",
number = "6",

}

RIS

TY - JOUR

T1 - A Systems-Based Map of Human Brain Cell-Type Enriched Genes and Malignancy-Associated Endothelial Changes

AU - Dusart, Philip

AU - Hallström, Björn Mikael

AU - Renné, Thomas

AU - Odeberg, Jacob

AU - Uhlén, Mathias

AU - Butler, Lynn Marie

N1 - Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2019/11/5

Y1 - 2019/11/5

N2 - 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.

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 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.

U2 - 10.1016/j.celrep.2019.09.088

DO - 10.1016/j.celrep.2019.09.088

M3 - SCORING: Journal article

C2 - 31693905

VL - 29

SP - 1690-1706.e4

JO - CELL REP

JF - CELL REP

SN - 2211-1247

IS - 6

ER -