The hematopoietic system is a cell renewal system in which mature peripheral blood cells with a limited life span are continuously replenished by proliferation and differentiation of lineage-specific progenitor cells derived from scarce pluripotent hematopoietic stem cells. The process of blood cell formation, hematopoiesis, takes approximately 20-30 cell divisions and takes mainly place in the bone marrow (BM) in adult mammals. In fetal hematopoiesis, liver and spleen also play an important role, whereas there is still residual hematopoiesis in the spleen of adult mice. The process of hematopoiesis is tightly controlled by hormone like proteins the hematopoietic growth factors (HGFs), by other cytokines, by complex interactions between hematopoietic cells and stromal cells in the BM, via extracellular matrix molecules and cell-cell interactions through specialized adhesion molecules. Different models have been developed in which stem cell commitment and differentiation are described as either a stochastic/random process or in which stem cell fate is regulated by external stimul.

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F1nancial support for the publication of this thesis by Merck Sharp & Doh me BV, Pfizer BV, and Amgen BV is gratefully acknowledged.
B. Löwenberg (Bob)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam

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