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

Dusart, PhilipKTH,Science for Life Laboratory, SciLifeLab,Skolan för bioteknologi (BIO) (författare)

Export Date: 22 October 2018; Article; Correspondence Address: Butler, L.M.; Science for Life Laboratory, School of Biotechnology, Kungliga Tekniska Högskolan (KTH) Royal Institute of TechnologySweden; email: Lynn.Butler@ki.se. QC 20181127
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.

Fagerberg, LinnKTH,Science for Life Laboratory, SciLifeLab,Skolan för bioteknologi (BIO)(Swepub:kth)u1dglfid (författare)
Perisic, L.Karolinska Institutet (författare)
Civelek, M. (författare)
Struck, EikeKTH,Skolan för bioteknologi (BIO),Science for Life Laboratory, SciLifeLab(Swepub:kth)PI000000 (författare)
Hedin, U.Karolinska Institutet (författare)
Uhlén, MathiasKTH,Science for Life Laboratory, SciLifeLab,Skolan för bioteknologi (BIO)(Swepub:kth)u1dulvmw (författare)
Trégouët, D. -A (författare)
Renné, T. (författare)
Odeberg, JacobKarolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab,Skolan för bioteknologi (BIO),Coagulation Unit, Centre for Hematology, Karolinska University Hospital, SE-171 76, Stockholm, Sweden(Swepub:kth)u1e4yljo (författare)
Butler, Lynn M.Karolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab,Skolan för bioteknologi (BIO),Clinical Chemistry and Blood Coagulation, Department of Molecular Medicine and Surgery, Karolinska Institute, SE-171 76, Stockholm, Sweden Institute for Clinical Chemistry and Laboratory Medicine, University Medical Centre Hamburg-Eppendorf, D-20246, Hamburg, Germany(Swepub:kth)u1tkjrxa (författare)
KTHScience for Life Laboratory, SciLifeLab (creator_code:org_t)

Av författaren/redakt...: Dusart, Philip; Fagerberg, Linn; Perisic, L.; Civelek, M.; Struck, Eike; Hedin, U.; visa fler...; Uhlén, Mathias; Trégouët, D. -A; Renné, T.; Odeberg, Jacob; Butler, Lynn M.; visa färre...

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