A systems-approach reveals human nestin is an endothelial-enriched, angiogenesis-independent intermediate filament protein

Sci Rep. 2018 Oct 2;8(1):14668. doi: 10.1038/s41598-018-32859-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aorta / cytology
  • Aorta / pathology
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / pathology
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Databases, Genetic / statistics & numerical data
  • Datasets as Topic
  • Endothelial Cells / metabolism*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Female
  • Gene Expression Profiling / methods
  • Haplotypes
  • Humans
  • Male
  • Neoplasms / pathology
  • Neovascularization, Pathologic / pathology
  • Nestin / physiology*
  • Polymorphism, Single Nucleotide
  • Primary Cell Culture
  • Proteomics / methods
  • Quantitative Trait Loci
  • RNA, Small Interfering / metabolism
  • Systems Biology / methods*
  • Tissue Array Analysis / methods


  • NES protein, human
  • Nestin
  • RNA, Small Interfering