A systems-approach reveals human nestin is an endothelial-enriched, angiogenesis-independent intermediate filament protein.
Philip DusartLinn FagerbergLjubica PerisicMete CivelekEike StruckUlf HedinMathias UhlenDavid Alexandre TrégouëtThomas RennéJacob OdebergLynn M ButlerPublished in: Scientific reports (2018)
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.
Keyphrases
- endothelial cells
- cardiovascular disease
- binding protein
- protein protein
- single cell
- high glucose
- stem cells
- signaling pathway
- amino acid
- poor prognosis
- gene expression
- induced pluripotent stem cells
- dna methylation
- aortic valve
- pulmonary artery
- coronary artery
- pulmonary arterial hypertension
- cancer therapy
- cardiovascular events
- atrial fibrillation
- wound healing
- childhood cancer
- cardiovascular risk factors
- data analysis