| 1. |
- Butler, L. M., et al.
(författare)
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Analysis of Body-wide Unfractionated Tissue Data to Identify a Core Human Endothelial Transcriptome
- 2016
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Ingår i: Cell Systems. - : Cell Press. - 2405-4712. ; 3:3, s. 287-301.e3
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial cells line blood vessels and regulate hemostasis, inflammation, and blood pressure. Proteins critical for these specialized functions tend to be predominantly expressed in endothelial cells across vascular beds. Here, we present a systems approach to identify a panel of human endothelial-enriched genes using global, body-wide transcriptomics data from 124 tissue samples from 32 organs. We identified known and unknown endothelial-enriched gene transcripts and used antibody-based profiling to confirm expression across vascular beds. The majority of identified transcripts could be detected in cultured endothelial cells from various vascular beds, and we observed maintenance of relative expression in early passage cells. In summary, we describe a widely applicable method to determine cell-type-specific transcriptome profiles in a whole-organism context, based on differential abundance across tissues. We identify potential vascular drug targets or endothelial biomarkers and highlight candidates for functional studies to increase understanding of the endothelium in health and disease.
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| 2. |
- Dusart, Philip, et al.
(författare)
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A systems-approach reveals human nestin is an endothelial-enriched, angiogenesis-independent intermediate filament protein
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The intermediate filament protein nestin is expressed during embryonic development, but considered largely restricted to areas of regeneration in the adult. Here, we perform a body-wide transcriptome and protein-profiling analysis to reveal that nestin is constitutively, and highly-selectively, expressed in adult human endothelial cells (EC), independent of proliferative status. Correspondingly, we demonstrate that it is not a marker for tumour EC in multiple malignancy types. Imaging of EC from different vascular beds reveals nestin subcellular distribution is shear-modulated. siRNA inhibition of nestin increases EC proliferation, and nestin expression is reduced in atherosclerotic plaque neovessels. eQTL analysis reveals an association between SNPs linked to cardiovascular disease and reduced aortic EC nestin mRNA expression. Our study challenges the dogma that nestin is a marker of proliferation, and provides insight into its regulation and function in EC. Furthermore, our systems-based approach can be applied to investigate body-wide expression profiles of any candidate protein.
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| 3. |
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| 4. |
- Gustafsson, K. L.R., et al.
(författare)
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Human cytomegalovirus replication induces endothelial cell interleukin-11
- 2018
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Ingår i: Cytokine. - : ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. - 1043-4666 .- 1096-0023. ; 111, s. 563-566
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial cells (EC) are critical sites of human cytomegalovirus (hCMV) infection in vivo. Infection can induce the production of various EC cytokines, such as interleukin (IL-)6, which can have autocrine and/or paracrine effector functions. Here, we report that hCMV induces the production of EC IL-11, a relatively understudied member of the IL-6-type cytokine family. We detail temporal EC IL-11 translation and protein secretion dynamics in response to hCMV infection, and reveal distinct differences compared to EC IL-6. Viral replication had markedly opposing effects on the regulation of these closely related cytokines, representing a major driving force behind IL-11 production, whilst concurrently suppressing IL-6 expression. This is the first report of any biological agent that stimulates EC IL-11 production.
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