Direct cell-cell communication in the blood-forming system.

In mammals, bone marrow is the principal tissue where blood is formed during adult life. Paracrine factors are generally considered to control this process but there is considerable evidence that gap junctions are present in haemopoietic tissues. Gap junctions have been implicated in developmental and patterning roles, and we set out to characterize the cells which are coupled, and to provide evidence for their role(s) in blood cell formation. Direct cell-cell communication, shown by dye-transfer, occurs between haemopoietic cells and certain stromal cells. In culture these stromal cells form a mat in which they retain their dye-coupling properties. Freeze-fracture electron microscopy confirms that this coupling is via gap junctions. When haemopoietic cells are cultured on top of these mats dye spreads upwards from the stromal cells into the haemopoietic cells above. Experiments in which haemopoietic cells were cultured alone, with stromal cell conditioned medium, or in direct contact with stromal cell underlays, were therefore carried out. The results of these experiments provide evidence that gap junctional communication may be playing a vital role in maintaining populations of precursor cells which would otherwise differentiate into end cells, leading to the ultimate demise of the system.