PDGF Receptor Alpha+ Mesoderm Contributes to Endothelial and Hematopoietic Cells in Mice. Issue 3 (13th February 2013)

• Record Type: Journal Article
• Authors: Ding, Guo; Tanaka, Yosuke; Hayashi, Misato; Nishikawa, Shin‐Ichi; Kataoka, Hiroshi
• Is Part Of: Developmental dynamics. Volume 242:Issue 3(2013:Mar.)
• Page Start: 254
• Page End: 268
• Publication Date: 2013-02-13
• Subjects: Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.23923
• Languages: English
• ISSNs: 1058-8388

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <underline>Background:</underline> 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. <underline>Results:</underline> 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 <italic>Etv2</italic> or restoration of <italic>Runx1</italic> in PDGFRα+ cells. <italic>Etv2</italic> deletion and <italic>Runx1</italic> restoration in PDGFRα+ cells resulted in abnormal vascular remodeling and rescue of fetal liver CD45+ and Lin‐Kit+Sca‐1+ (KSL) cells, respectively. <underline>Conclusions:</underline> 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. <italic>Developmental Dynamics 242:254–268, 2013</italic>. © 2013 Wiley Periodicals, Inc.</p> </abstract>