Abstract
Fibronectin is a ubiquitous extracellular matrix protein that is produced by many cell types in the bone marrow and distributed throughout it. Cells of the stem cell niche produce the various isoforms of this protein. Fibronectin not only provides the cells a scaffold to bind to, but it also modulates their behavior by binding to receptors on the adjacent hematopoietic stem cells and stromal cells. These receptors, which include integrins such as α4β1, α9β1, α4β7, α5β1, αvβ3, Toll-like receptor-4 (TLR-4), and CD44, are found on the hematopoietic stem cell. Because the knockout of fibronectin is lethal during embryonal development and because fibronectin is produced by almost all cell types in mammals, the study of its role in hematopoiesis is difficult. Nevertheless, strong and direct evidence exists for its stimulation of myelopoiesis and thrombopoiesis using in vivo models. Other reviewed effects can be deduced from the study of fibronectin receptors, which showed their activation modifies the behavior of hematopoietic stem cells. Erythropoiesis was only stimulated under hemolytic stress, and mostly late stages of lymphocytic differentiation were modulated. Because fibronectin is ubiquitously expressed, these interactions in health and disease need to be taken into account whenever any molecule is evaluated in hematopoiesis.
Highlights
The bone marrow represents a unique environment optimized for hematopoiesis
Fibronectin mostly binds to integrins, which consist of heterodimers of an α and a β subunit located on the cell surface
We present first the evidence of the role of integrins in hematopoiesis followed by a discussion of the effects of fibronectin and fibronectin-binding receptors on stem cell behavior: Migration and homing, attachment and retention, proliferation, and differentiation
Summary
The bone marrow represents a unique environment optimized for hematopoiesis. On one hand, hematopoietic stem cells in the marrow need to be preserved throughout life, and on the other hand, they need to respond to acute changes in the requirement for various types of blood cells. A variety of cells are located in close proximity of the stem cells, providing them with a protective environment, and with short-distance signals to allow them to function This niche was initially thought to be close to the bone lining cells or osteoblasts [1], but later work seems to localize the long-term hematopoietic stem cells in proximity to endothelial cells [2,3]. All these cells are embedded in a meshwork of extracellular matrix proteins produced by the supportive cells. The matrix serves as a reservoir for growth factors changing their availability depending on its composition [4]
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