PDGF receptor alpha+ mesoderm contributes to endothelial and hematopoietic cells in mice

Guo Ding1, Yosuke Tanaka, Misato Hayashi

  • 1Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Kobe, Japan.

Abstract

Insights

Early mesoderm, specifically the PDGFRα+ population, can develop into endothelial and hematopoietic cells in mouse embryos. This finding highlights the crucial role of PDGFRα+ mesoderm in vascular and blood development.

Area of Science:

  • Developmental biology
  • Hematopoiesis
  • Vascular biology

Background:

  • Early mesoderm differentiates into Flk-1+ (lateral) and PDGFRα+ (paraxial) populations.
  • Endothelial cells (ECs) and hematopoietic progenitor cells (HPCs) are known to derive from Flk-1+ cells.
  • The potential of PDGFRα+ cells to generate hemato-endothelial lineages in vivo remained unproven.

Purpose of the Study:

  • To investigate whether PDGFRα+ early mesoderm can contribute to hemato-endothelial lineages in mouse embryos.
  • To determine the functional significance of PDGFRα+ mesoderm in vascular development and hematopoiesis.

Main Methods:

  • Utilized PDGFRαMerCreMer mice for genetic lineage tracing.
  • Analyzed contributions to endothelial cells, hemogenic ECs, B lymphocytes, and Lin-Kit+Sca-1+ (KSL) cells.
  • Performed genetic manipulation (Etv2 deletion, Runx1 restoration) within PDGFRα+ cells.

Main Results:

  • PDGFRα+ mesoderm contributes to endothelial cells, including hemogenic ECs, fetal liver B lymphocytes, and KSL cells.
  • Contribution of PDGFRα+ mesoderm to ECs and HPCs was limited until embryonic day 8.5.
  • Genetic deletion of Etv2 in PDGFRα+ cells caused abnormal vascular remodeling, while Runx1 restoration rescued fetal liver CD45+ and KSL cells.

Conclusions:

  • PDGFRα+ early mesoderm is a source of endothelial and hematopoietic cells in mouse embryos.
  • PDGFRα+ mesoderm plays a functionally significant role in both vascular development and hematopoiesis.