Differentiation of hemopoietic stem cells in the thymus

Encased within the bones of the body, there exists an organ system, the bone marrow, in which a large number of different cell types develops. Most bone marrow (BM) cells belong to the hemopoietic and lymphatic lineages (i.e. erythrocytes, platelets, granulocytes, macrophages and lymphocytes). Other cell types have also been shown to be derived from precursor cells that are present in the BM: tissue mast cells (Kitamura et al., 1977 and 1981), dendritic cells (Steinman et al., 1974; Pugh et al, 1983), Kupffer cells (van Furth, 1980; Bouwens and Wisse, 1980) and osteoclasts (Ash et al, 1980). The bone marrow is thus a source of cells which have a wide variety of functions and which can be found in many tissues of the body. Most BM cells are mature cells. Although the mature cells are important for the homeostasis of the body, they will not be considered in this thesis. Many experiments have been and still are performed with the intention to characterize and isolate the cell(s) that give rise to the above mentioned mature cell types. The concept of a pluripotent hemopoietic stem cell {PHSC) has arisen from these experiments. It has been hypothesized that the PHSC, after the proper stimulation, can give rise to all BM derived cell types. Another important characteristic of the PHSC is its capacity for self renewal. This will be discussed below. Other experiments have pointed to the existence of cells in the BM that have only a limited capacity for differentiating and self renewal potential when compared to the PHSC. These "restricted" stem cells can only give rise to descendants in one or two closely related differentiation pathways. These stem cells are often referred to as progenitor cells or committed precursor cells and as uni(or bi)potent hemopoietic stem cells. This stem cell type receives little attention in this thesis.

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