A Role for the Long Noncoding RNA SENCR in Commitment and Function of Endothelial Cells

Mounia Boulberdaa, Elizabeth Scott*, Margaret Ballantyne, Raquel Garcia, Betty Descamps, Gianni D. Angelini, Mairi Brittan, Amanda Hunter, Martin McBride, John McClure, Joseph M. Miano, Costanza Emanueli, Nicholas L. Mills, Joanne C. Mountford, Andrew H. Baker

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

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Abstract

Despite the increasing importance of long noncoding 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 noncoding 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 hemogenic 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 human umbilical endothelial cell (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.Molecular Therapy (2016).
Original languageEnglish
Pages (from-to)978-990
Number of pages13
JournalMolecular Therapy
Volume24
Issue number5
DOIs
Publication statusPublished - May 2016

Structured keywords

  • Centre for Surgical Research

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    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., & Baker, A. H. (2016). A Role for the Long Noncoding RNA SENCR in Commitment and Function of Endothelial Cells. Molecular Therapy, 24(5), 978-990. https://doi.org/10.1038/mt.2016.41