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Open Access Highly Accessed Research article

ERG is required for the differentiation of embryonic stem cells along the endothelial lineage

Vesna Nikolova-Krstevski124, Lei Yuan124, Alexandra Le Bras124, Preethi Vijayaraj124, Maiko Kondo124, Isabel Gebauer124, Manoj Bhasin3, Chris V Carman24 and Peter Oettgen124*

Author Affiliations

1 Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA 02215, USA

2 Division of Molecular and Vascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA 02215, USA

3 Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA 02215, USA

4 Department of Medicine, and the Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA 02215, USA

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BMC Developmental Biology 2009, 9:72  doi:10.1186/1471-213X-9-72

Published: 23 December 2009

Abstract

Background

The molecular mechanisms that govern stem cell differentiation along the endothelial lineage remain largely unknown. Ets related gene (ERG) has recently been shown to participate in the transcriptional regulation of a number of endothelial specific genes including VE-cadherin (CD144), endoglin, and von Willebrand's Factor (vWF). The specific role of the ETS factor ERG during endothelial differentiation has not been evaluated.

Results

ERG expression and function were evaluated during the differentiation of embryonic stem cells into embryoid bodies (EB). The results of our study demonstrate that ERG is first expressed in a subpopulation of vascular endothelial growth factor receptor 2 (VEGF-R2) expressing cells that also express VE-cadherin. During ES cell differentiation, ERG expression remains restricted to cells of the endothelial lineage that eventually coalesce into primitive vascular structures within embryoid bodies. ERG also exhibits an endothelial cell (EC)-restricted pattern during embryogenesis. To further define the role of ERG during ES cell differentiation, we used a knockdown strategy to inhibit ERG expression. Delivery of three independent shRNA led to 70-85% reductions in ERG expression during ES cell differentiation compared to no change with control shRNA. ERG knockdown was associated with a marked reduction in the number of ECs, the expression of EC-restricted genes, and the formation of vascular structures.

Conclusion

The ETS factor ERG appears to be a critical regulator of EC differentiation.