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

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.

Mechanotransductive Differentiation of Hair Follicle Stem Cells Derived from Aged Eyelid Skin into Corneal Endothelial-Like Cells

“…1B, all measured markers were expressed. The co-localized expression of pluripotency transcription factor Oct-4 with Nestin an intermediate filament of stem or progenitor cells [23] as well as the expression of the gap junction protein Connexin-43 [24,25] as a postulated marker for pre-migratory and migratory neural crest stem cells with the stage-specific embryonic antigen-4 (SSEA-4) a glycosphingolipid marker commonly known to be expressed in pluripotent cells which is downregulated through differentiation [26], supported the hypothesis of an immature stem cell population present in the hair follicle tissue region. This was further confirmed by the co-localized expression of CD34 with CD49f, which have been shown to be key modulators of HFSC identity in vitro [27].…”

High NESTIN Expression Marks the Endosteal Capillary Network in Human Bone Marrow

“…Despite a consistent number of observations in animal models, NESTIN expression is still poorly investigated in humans. Dusart et al (2018) recently reported data from transcriptome and antibody-based analysis of tissue microarrays (TMA) form adult human organs. This study revealed body-wide NESTIN expression in the ECs, both in normal and tumor tissues, independently from their proliferative status and debating the idea of NESTIN as neo-vascularization associated marker ( Suzuki et al, 2010 ; Matsuda et al, 2013 ).…”

Evaluation of serum Nestin and HOTAIR rs12826786 C>T polymorphism as screening tools for breast cancer in Egyptian women

“…Also, they reported high expression of Nestin in EC across several organs among them was the breast, challenging the previous knowledge of the restricted expression and stemness of Nestin. Furthermore, they observed a lower expression of Nestin in EC of bladder urothelial carcinoma and lung adenocarcinoma tissue than in corresponding normal tissue, further demonstrating that Nestin is not associated specifically with EC of tumors (15).…”

“…Furthermore, a recent study found a positive correlation between Nestin mRNA and Nestin protein expression in germline BRCA1 related breast cancer, a basal-like phenotype, with reduced survival, and stem ness characteristics (14). The marker expression was reported in endothelial cells of breast as well (15). So far, Nestin has been evaluated in breast cancer patients only on a tissue level using an immunohistochemistry technique for diagnostic and prognostication purposes.…”