Hematopoiesis is the deterministic process of blood cell formation taking place in the bone marrow. Mature blood cells are produced by a tightly controlled mechanism from hematopoietic stem cells (HSCs) residing in the bone marrow. Upon maturation blood cells are released into the peripheral blood and from this point onward can be transported to the different locations of the body. The mature blood cells exert different functions dependent on a strictly controlled path of maturation. The distinct leukocytes comprising granulocytes, monocytes, macrophages, natural killer cells and lymphocytes are essential for the defense against pathogens and foreign invaders, erythrocytes play a pivotal role in the transportation of oxygen to remote organs, and platelets confer the process of blood clotting. Mature blood cells are short-lived and require continuous replenishment. The control of the production and the total number of blood cells is conferred by multipotent progenitors and a small population of pluripotent HSCs (Figure 1). HSCs reside in the bone marrow of adult mammals at the apex of a hierarchy of progenitors which become progressively restricted to several and eventually single lineages of blood cells. Additionally these pluripotent stem cells have the unique ability to self-renew, generating a source for continuous replenishment of the complete blood cell system. The hematopoietic stem cell compartment contains stem cells with progressively decreased self-renewal capacity with the retention of multi-lineage reconstitution. The rare long term HSC (LT-HSC) is at the pinnacle of the hematopoietic hierarchy and is mainly quiescent. With the most conserved rate of self-renewal it prevents the depletion of the stem cell pool. The less rare short term HSC (ST-HSC) still retains a minimal ability for self-renewal and is the more active effector cell for hematopoietic replenishment in normal situations. The main constituent of the hematopoietic stem cell compartment is the multipotent progenitor (MPP) which lost its self-renewal capacity, however, kept the ability to give rise to daughter cells of different lineages. The daughter cells, common myeloid progenitor (CMP) and common lymphoid progenitor (CLP), are still oligopotent as they give rise to multiple blood cell types, e.g., lymphocytes, granulocytes, platelets and erythrocytes. The production of mature blood cells is a strictly controlled process that adapts to the needs of human physiology, e.g., erythrocyte production after blood loss. The control is asserted mainly by external stimuli, e.g., hematopoietic cytokines or growth factors, which are produced by constituents of the regulatory microenvironment within the bone marrow niche, other blood cells or cytokine secreting organs. The microenvironment plays a pivotal role in the formation of adequate numbers of blood cells of the correct type and the hematopoietic cytokines it produces allows the hematopoietic system to dynamically adapt to extramedullary events, e.g., blood loss, infection or cancer immunoediting.

, , , ,
H.R. Delwel (Ruud) , B. Löwenberg (Bob)
Erasmus University Rotterdam
The work described in this thesis was performed at the Department of Hematology at the Erasmus University Medical Center, Rotterdam, The Netherlands. The work was funded by the Center for Translational Molecular Medicine.
hdl.handle.net/1765/77558
Erasmus MC: University Medical Center Rotterdam

Sanders, M. (2015, February 17). Computational Biology-Driven Genomic and Epigenomic Delineation of Acute Myeloid Leukemia. Retrieved from http://hdl.handle.net/1765/77558