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

Dusart, PhilipKTH,Cellulär och klinisk proteomik,Science for Life Laboratory, SciLifeLab (författare)

QC 20191126. QC 20200109
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.

Hallström, Björn M.KTH,Proteinvetenskap,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1ih19oh (författare)
Renne, ThomasUniv Med Ctr Hamburg Eppendorf, Inst Clin Chem & Lab Med, D-20246 Hamburg, Germany. (författare)
Odeberg, Jacob,Professor,1963-Karolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap(Swepub:kth)u1e4yljo (författare)
Uhlén, MathiasKTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap(Swepub:kth)u1dulvmw (författare)
Butler, Lynn M.Karolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab,Cellulär och klinisk proteomik(Swepub:kth)u1tkjrxa (författare)
KTHCellulär och klinisk proteomik (creator_code:org_t)

Av författaren/redakt...: Dusart, Philip; Hallström, Björn ...; Renne, Thomas; Odeberg, Jacob, ...; Uhlén, Mathias; Butler, Lynn M.

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