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

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25 Scopus citations


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
Pages (from-to)45-57
Number of pages13
JournalDevelopmental cell
Issue number1
StatePublished - Jul 17 2012
Externally publishedYes

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    Sturgeon, C. M., Chicha, L., Ditadi, A., Zhou, Q., McGrath, K. E., Palis, J., Hammond, S. M., Wang, S., Olson, E. N., & Keller, G. (2012). Primitive Erythropoiesis Is Regulated by miR-126 via Nonhematopoietic Vcam-1 + Cells. Developmental cell, 23(1), 45-57.