Haematopoiesis

Abstract Haematopoiesis generates a variety of distinct blood cell types from a common stem cell. Secreted signalling molecules called cytokines modulate the survival, proliferation and differentiation of all the blood cell lineages, mediated by defined sets of transcription factors. Haematopoiesis is also influenced by external cues such as oxygen concentration. Haematopoiesis is an ongoing process continuing throughout lifetime, although the location of stem cells, and the specific cell types derived from them, changes during embryonic, foetal and early postnatal development. In the adult, haematopoiesis occurs primarily in the bone marrow, in association with a supportive niche. Haematopoietic stem cells are derived from cells bipotential for blood and endothelial cells, or directly from specialised endothelium. Blood lineages have a hierarchical relationship, but there is some flexibility among progenitors for deriving specific fates. Defects in haematopoiesis result in common and serious human diseases including anaemia and leukaemia. Key Concepts Haematopoiesis is the process of forming blood cells, which occurs during embryogenesis and throughout life. Defects in haematopoiesis can result in some of the most common and serious human diseases, including anaemia and leukaemia. Blood consists of many different kinds of cells with a diverse range of functions, controlling gaseous exchange and clotting and comprising the immune system. All blood cells are derived from a common progenitor, the haematopoietic stem cell. The sites where haematopoiesis occurs change during embryonic development, but in adult mammals, the bone marrow is the major site of haematopoiesis. Haematopoietic stem cells in the bone marrow reside in a specialised microenvironment known as the haematopoietic stem cell niche, composed of osteoblasts, mesenchymal cells and sinusoidal vessels. Growth factors called cytokines control the survival, self‐renewal and differentiation of haematopoietic stem cells and their progeny. Blood cells have a close developmental relationship with endothelial cells, and haematopoietic stem cells appear to derive from ‘haemogenic endothelium’. Haematopoiesis is also regulated by external factors. For example, hypoxia results in a compensatory increase in the number of erythrocytes. Much effort is currently focused on generating and manipulating haematopoietic stem cells in vitro, to develop new regenerative therapies.