PDGF Receptor Alpha+ Mesoderm Contributes to Endothelial and Hematopoietic Cells in Mice

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+ cel...

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Published in:	Developmental dynamics 2013-03, Vol.242 (3), p.254-268
Main Authors:	Ding, Guo, Tanaka, Yosuke, Hayashi, Misato, Nishikawa, Shin‐Ichi, Kataoka, Hiroshi
Format:	Article
Language:	eng
Subjects:	Animals Cell Lineage - physiology Core Binding Factor Alpha 2 Subunit - genetics Core Binding Factor Alpha 2 Subunit - metabolism Embryo, Mammalian - cytology Embryo, Mammalian - metabolism endothelial Endothelial Cells - cytology Endothelial Cells - metabolism Flk‐1 hematopoiesis Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - metabolism Liver - blood supply Liver - cytology Liver - embryology Mesoderm - cytology Mesoderm - embryology Mice Mice, Transgenic PDGFRα Receptor, Platelet-Derived Growth Factor alpha - biosynthesis Receptor, Platelet-Derived Growth Factor alpha - genetics Runx1 Transcription Factors - genetics Transcription Factors - metabolism Vascular Endothelial Growth Factor Receptor-2 - genetics Vascular Endothelial Growth Factor Receptor-2 - metabolism
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Summary:	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. Key Findings: PDGF receptor alpha–positive mesoderm contributes to endothelial and hematopoietic cells in physiological mouse embryogenesis. PDGF receptor alpha–positive mesoderm in early embryo is distinct from yolk sac blood island mesoderm, representing a source of hematopoietic cells on the embryo proper side. Genetic manipulation of Etv2 or Runx1 in PDGF receptor alpha–positive mesoderm demonstrates the functional significance of this mesoderm subset in vascular development and hematopoiesis.
ISSN:	1058-8388 1097-0177