Hematopoietic Progenitor and Stem Cell Regulation during Development: Hypoxia and Niches

In a healthy adult person, almost 1011 - 1012 new blood cells are generated daily in order to maintain the steady state in peripheral circulation (Paul, 2008). To this end, a high level of self-renewal and differentiation of Hematopoietic stem cells (HSCs) is required. HSCs have the unique ability of self-renewal to maintain the stem cell pool. They also differentiate to more committed progenitors which produce all mature blood cell lineages (Lemischka, 1992; Medvinsky and Dzierzak, 1998; Orkin, 2000). In general, there are two main branches in the adult hematopoietic hierarchy: The lymphoid branch is derived from common lymphoid progenitors that mature to B-cells and T-cells. Lymphocytes are involved in the adaptive immune system. The myeloid branch is derived from common myeloid progenitor cells that give rise to more lineage-restricted precursors. These progenitors differentiate into the following cell types: erythrocytes, the most abundant terminally differentiated cells in the blood, which are required for oxygen transport, as well as megakaryocytes, involved in blood clotting and granulocytes and macrophages, which are involved in innate immunity. Recent insights into understanding HSC regulation have facilitated HSC clinical therapies and trials for hematological disorders. Despite progress in this field, there remain difficulties in ex vivo expansion of HSCs on a scale that ensures efficient regeneration of blood system. Overcoming this challenge calls for a more information on the intrinsic and extrinsic factors that regulate development, maintenance, and function of HSCs