A role for the long non-coding RNA SENCR in commitment and function of endothelial cells

Boulberdaa, M. et al. (2016) A role for the long non-coding RNA SENCR in commitment and function of endothelial cells. Molecular Therapy, 24(5), pp. 978-990. (doi:10.1038/mt.2016.41) (PMID:26898221) (PMCID:PMC4876031)

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Abstract

Despite the increasing importance of long non-coding RNA in physiology and disease, their role in endothelial biology remains poorly understood. Growing evidence has highlighted them to be essential regulators of human embryonic stem cell differentiation. SENCR, a vascular-enriched long non-coding RNA, overlaps the Friend Leukemia Integration virus 1 (FLI1) gene, a regulator of endothelial development. Therefore, we wanted to test the hypothesis that SENCR may contribute to mesodermal and endothelial commitment as well as in endothelial function. We thus developed new differentiation protocols allowing generation of endothelial cells from human embryonic stem cells using both directed and haemogenic routes. The expression of SENCR was markedly regulated during endothelial commitment using both protocols. SENCR did not control the pluripotency of pluripotent cells; however its overexpression significantly potentiated early mesodermal and endothelial commitment. In HUVEC, SENCR induced proliferation, migration and angiogenesis. SENCR expression was altered in vascular tissue and cells derived from patients with critical limb ischemia and premature coronary artery disease compared to controls. Here, we showed that SENCR contributes to the regulation of endothelial differentiation from pluripotent cells and controls the angiogenic capacity of HUVEC. These data give novel insight into the regulatory processes involved in endothelial development and function.

Item Type:Articles
Additional Information:Further funding from British Heart Foundation Centre for Vascular Reparation grant (RM/13/1/30158) to University of Edinburgh.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Baker, Professor Andrew and Garcia, Dr Raquel and Mountford, Dr Joanne and McBride, Dr Martin and Boulberdaa, Dr Mounia and McClure, Dr John
Authors: Boulberdaa, M., Scott, E., Ballantyne, M., Garcia, R., Descamps, B., Angelini, G. D., Brittan, M., Hunter, A., McBride, M., McClure, J., Miano, J. M., Emanueli, C., Mills, N. L., Mountford, J. C., and Baker, A. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Molecular Therapy
Publisher:Nature Publishing Group
ISSN:1525-0016
ISSN (Online):1525-0024
Copyright Holders:Copyright © 2016 The American Society of Gene & Cell Therapy
First Published:First published in Molecular Therapy 24(5): 978-990
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
531341In vitro and in vivo analysis of stem cell commitment to vascular endothelial cellsAndrew BakerBritish Heart Foundation (BHF)SP/10/005/28298RI CARDIOVASCULAR & MEDICAL SCIENCES