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

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 initi...

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Bibliographic Details
Published in:Developmental cell 2012-07, Vol.23 (1), p.45-57
Main Authors: Sturgeon, Christopher M., Chicha, Laurie, Ditadi, Andrea, Zhou, Qinbo, McGrath, Kathleen E., Palis, James, Hammond, Scott M., Wang, Shusheng, Olson, Eric N., Keller, Gordon
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell differentiation, maturation, development, hematopoiesis
Cell Line
Cell physiology
Coculture Techniques
Embryonic Stem Cells - cytology
Embryonic Stem Cells - physiology
Erythroblasts - cytology
Erythroblasts - physiology
Erythroid Precursor Cells - cytology
Erythroid Precursor Cells - physiology
Erythropoiesis - genetics
Erythropoiesis - physiology
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Developmental - physiology
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - metabolism
Mesenchymal Stromal Cells - physiology
Mice
MicroRNAs - physiology
Molecular and cellular biology
Osteoblasts - cytology
Osteoblasts - physiology
Vascular Cell Adhesion Molecule-1 - biosynthesis
Vascular Cell Adhesion Molecule-1 - genetics
Vascular Cell Adhesion Molecule-1 - metabolism
Vascular Endothelial Growth Factor A - metabolism
Vascular Endothelial Growth Factor A - physiology
Vascular Endothelial Growth Factor Receptor-2 - metabolism
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Summary: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. [Display omitted] ► Primitive erythropoiesis is a tightly regulated developmental program ► miR-126 regulates EryP colony-forming cell (CFC) potential both in vitro and in vivo ► miR-126 regulates mesenchymal Vcam-1, which controls EryP-CFC cell nonautonomously ► Vcam-1 represses EryP-CFC by inducing maturation to erythroblasts via a Src kinase Primitive erythropoiesis is a transient, tightly regulated developmental program. Sturgeon et al. elucidate the rapid termination of this lineage using an embryonic stem cell differentiation system. They show that miR-126 terminates the expression of Vcam-1 on mesenchymal cells, triggering maturation and depletion of erythroid progenitors in a cell nonautonomous manner.
ISSN:1534-5807
1878-1551
DOI:10.1016/j.devcel.2012.05.021