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

Area of Science:

• Vascular biology
• Stem cell biology
• RNA biology

Background:

• Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in physiology and disease.
• The specific functions of lncRNAs in endothelial cell biology are not well understood.
• SENCR, a lncRNA enriched in vascular tissues, is located near the FLI1 gene, a key regulator of endothelial development.

Purpose of the Study:

• To investigate the role of SENCR in endothelial cell differentiation from human embryonic stem cells.
• To determine SENCR's impact on endothelial cell function, including proliferation, migration, and angiogenesis.
• To examine SENCR expression in vascular diseases.

Main Methods:

• Developed novel differentiation protocols for generating endothelial cells from human embryonic stem cells via directed and hemogenic routes.
• Analyzed SENCR expression during endothelial commitment.
• Overexpressed SENCR in human umbilical endothelial cells (HUVECs) to assess its functional effects.
• Examined SENCR levels in vascular tissues and cells from patients with critical limb ischemia and premature coronary artery disease.

Main Results:

• SENCR expression was significantly regulated during endothelial commitment using both differentiation protocols.
• SENCR overexpression potentiated early mesodermal and endothelial commitment but did not affect pluripotency.
• SENCR induced proliferation, migration, and angiogenesis in HUVECs.
• Altered SENCR expression was observed in vascular tissues from patients with critical limb ischemia and premature coronary artery disease.

Conclusions:

• SENCR plays a crucial role in regulating endothelial differentiation from pluripotent stem cells.
• SENCR enhances the angiogenic capacity of endothelial cells.
• These findings provide new insights into the molecular mechanisms governing endothelial development and function.