title: A Role for the Long Noncoding RNA SENCR in Commitment and Function of Endothelial Cells.
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.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.|BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Mounia
authors.initials: M
authors.lastname: Boulberdaa
authors.affiliation: Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Scott
authors.affiliation: Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: Margaret
authors.initials: M
authors.lastname: Ballantyne
authors.affiliation: Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: Raquel
authors.initials: R
authors.lastname: Garcia
authors.affiliation: Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Betty
authors.initials: B
authors.lastname: Descamps
authors.affiliation: Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, UK.|National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Gianni D
authors.initials: GD
authors.lastname: Angelini
authors.affiliation: BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Mairi
authors.initials: M
authors.lastname: Brittan
authors.affiliation: BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Hunter
authors.affiliation: Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: McBride
authors.affiliation: Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: John
authors.initials: J
authors.lastname: McClure
authors.affiliation: Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, New York, New York, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Miano
authors.affiliation: Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, UK.|National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Costanza
authors.initials: C
authors.lastname: Emanueli
authors.affiliation: BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Mills
authors.affiliation: Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.|Research, Development & Innovation, Scottish National Blood Transfusion Service, Ellen's Glen Road, Edinburgh, UK.
authors.forename: Joanne C
authors.initials: JC
authors.lastname: Mountford
authors.affiliation: Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.|BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Baker
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009389:Neovascularization, Pathologic / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D062085:RNA, Long Noncoding; C000620398:long noncoding RNA SENCR, human