Primitive Erythropoiesis Is Regulated by miR-126 via Nonhematopoietic Vcam-1 + Cells

Christopher M. Sturgeon, Laurie Chicha, Andrea Ditadi, Qinbo Zhou, Kathleen E. McGrath, James Palis, Scott M. Hammond, Shusheng Wang, Eric N. Olson, Gordon Keller

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Primitive erythropoiesis defines the onset of hematopoiesis in the yolk sac of the early embryo and is initiated by the emergence of progenitors assayed as colony-forming cells (EryP-CFCs). EryP-CFCs are detected for only a narrow window during embryonic development, suggesting that both their initiation and termination are tightly controlled. Using the embryonic stem differentiation system to model primitive erythropoiesis, we found that miR-126 regulates the termination of EryP-CFC development. Analyses of miR-126 null embryos revealed that this miR also regulates EryP-CFCs in vivo. We identified vascular cell adhesion molecule-1 (Vcam-1) expressed by a mesenchymal cell population as a relevant target of miR-126. Interaction of EryP-CFCs with Vcam-1 accelerated their maturation to ßh1-globin + and Ter119 + cells through a Src family kinase. These findings uncover a cell nonautonomous regulatory pathway for primitive erythropoiesis that may provide insight into the mechanism(s) controlling the developmental switch from primitive to definitive hematopoiesis.

Original languageEnglish (US)
Pages (from-to)45-57
Number of pages13
JournalDevelopmental cell
Volume23
Issue number1
DOIs
StatePublished - Jul 17 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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