Investigations of how does the haematopoietic stem cell generate the different types of blood cells

For many years the mammalian blood cell system has provided cell biologists and haematologists with one of the best experimental models in which to unravel how one stem cell – the haematopoietic stem cell – gives rise to the many different types of cells of the blood and immune systems. Laboratory work aims to meet the need to revise textbook accounts of the generation of blood cells. We have provided a new, and highly regarded, model for blood cell development. The 30 year old ‘classic’ model of haematopoiesis states there are two families of cells, namely myeloid/erythroid and lymphoid. The model we favour refutes this viewpoint. We have proposed there is a series of pair-wise relationships between all lineage fates – a fate choice continuum. We test this model by examining various primitive haematopoietic progenitor cells to see whether there is a pattern to sub-sets of lineage potentials within single cells that fits with placing cell lineages adjacent in our pair-wise model. Ongoing studies are also looking at the mechanisms that govern the commitment of haematopoietic stem cells to becoming one particular type of cell. Endeavours to understand the controls that drive the maturation of committed cells to functional end cells are focussed on signals that arise from differentiating agents such as all-trans retinoic acid and vitamin D3. We are also interested in the use of novel retinoid analogs to modulate haematopoiesis and to treat malignancies.

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