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Ephrin ligands and Eph receptors contribution to hematopoiesis

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Abstract

Hematopoietic stem and progenitor cells reside predominantly in the bone marrow. They supply billions of mature blood cells every day during life through maturation into multilineage progenitors and self-renewal. Newly produced mature cells serve to replenish the pool of circulating blood cells at the end of their life-span. These mature blood cells and a few hematopoietic progenitors normally exit the bone marrow through the sinusoidal vessels, a specialized venous vascular system that spreads throughout the bone marrow. Many signals regulate the coordinated mobilization of hematopoietic cells from the bone marrow to the circulation. In this review, we present recent advances on hematopoiesis and hematopoietic cell mobilization with a focus on the role of Ephrin ligands and their Eph receptors. These constitute a large family of transmembrane ligands and receptors that play critical roles in development and postnatally. New insights point to distinct roles of ephrin and Eph in different aspects of hematopoiesis.

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Abbreviations

HSPCs:

Hematopoietic stem/progenitor cells

CAR:

(CXCL12-abundant reticular)

Tgfβ:

Transforming growth factor β

ROS:

Reactive oxygen species

G-CSF:

Granulocyte colony-stimulating factor

WHIM:

Warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis

VCAM-1:

Vascular cell adhesion molecule-1

Kit-L:

Kit ligand

MMP9:

Matrix metallopeptidase-9

GPI:

Glycophoshosphatidylinositol

FGFR:

Fibroblast growth factor receptor

PDGFR:

Platelet-derived growth factor receptor

SH2:

Src homology 2

PI3K:

Phosphoinositide 3-kinase

GEFs:

Guanosine exchange factors

VEGF:

Vascular endothelial growth factor

VEGFR2:

VEGF receptor-2

ES cells:

Embryonic stem cells

SVZ:

Subventricular zone

SGZ:

Subgranular zone

M-CSF:

Macrophage colony-stimulating factor

RANK-L:

RANK ligand

IGF:

Insulin-like growth factor

SDF1:

Stromal derived factor-1

LTC-IC:

Long-term culture initiating cells

IL-6:

Interleukin-6

FLT-3:

Fms-like tyrosine-protein kinase-3

VLA-4:

Very late antigen 4

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Acknowledgements

We thank the members of our laboratory, particularly Dr. Hyeongil Kwak, and our collaborators Drs. R. Weigert, J. L. Martinez-Torrecuadrada, M. Henkemeyer, M. C. Poulos and J. Butler for their contributions to this review.

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  1. Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 4124, Bethesda, MD, 20892, USA

    Giovanna Tosato

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Tosato, G. Ephrin ligands and Eph receptors contribution to hematopoiesis. Cell. Mol. Life Sci. 74, 3377–3394 (2017). https://doi.org/10.1007/s00018-017-2566-1

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