Guo Ding and Yosuke Tanaka contributed equally to this article.
PDGF Receptor Alpha+ Mesoderm Contributes to Endothelial and Hematopoietic Cells in Mice
Article first published online: 13 FEB 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 242, Issue 3, pages 254–268, March 2013
How to Cite
Ding, G., Tanaka, Y., Hayashi, M., Nishikawa, S.-I. and Kataoka, H. (2013), PDGF Receptor Alpha+ Mesoderm Contributes to Endothelial and Hematopoietic Cells in Mice. Dev. Dyn., 242: 254–268. doi: 10.1002/dvdy.23923
The authors declare no competing financial interests.
- Issue published online: 20 FEB 2013
- Article first published online: 13 FEB 2013
- Accepted manuscript online: 17 JAN 2013 10:42PM EST
- Manuscript Accepted: 20 DEC 2012
- Manuscript Revised: 12 DEC 2012
- Manuscript Received: 10 OCT 2012
- PRESTO (Japan Science and Technology Agency)
- Leading Project for Realization of Regenerative Medicine and Ministry of Education, Culture, Sports, Science and Technology . Grant Number: 20590295
Background: Early mesoderm can be classified into Flk-1+ or PDGF receptor alpha (PDGFRα)+ population, grossly representing lateral and paraxial mesoderm, respectively. It has been demonstrated that all endothelial (EC) and hematopoietic (HPC) cells are derived from Flk-1+ cells. Although PDGFRα+ cells give rise to ECs/HPCs in in vitro ES differentiation, whether PDGFRα+ population can become hemato-endothelial lineages has not been proved in mouse embryos. Results: Using PDGFRαMerCreMer mice, PDGFRα+ early mesoderm was shown to contribute to endothelial cells including hemogenic ECs, fetal liver B lymphocytes, and Lin-Kit+Sca-1+ (KSL) cells. Contribution of PDGFRα+ mesoderm into ECs and HPCs was limited until E8.5, indicating that PDGFRα+/Flk-1+ population that exists until E8.5 may be the source for hemato-endothelial lineages from PDGFRα+ population. The functional significance of PDGFRα+ mesoderm in vascular development and hematopoiesis was confirmed by genetic deletion of Etv2 or restoration of Runx1 in PDGFRα+ cells. Etv2 deletion and Runx1 restoration in PDGFRα+ cells resulted in abnormal vascular remodeling and rescue of fetal liver CD45+ and Lin-Kit+Sca-1+ (KSL) cells, respectively. Conclusions: Endothelial and hematopoietic cells can be derived from PDGFRα+ early mesoderm in mice. PDGFRα+ mesoderm is functionally significant in vascular development and hematopoiesis from phenotype analysis of genetically modified embryos. Developmental Dynamics 242:254–268, 2013. © 2013 Wiley Periodicals, Inc.