Hematopoyesis

Chapter 5
Origin and Development of Blood Cells

The blood contains several different types of cells. Each of these cell types is quite distinct in appearance, and each has a specific biologic function. Erythrocytes are anucleate, biconcave discoid cells filled with hemoglobin, the major protein that binds oxygen. The erythrocytes transport the respiratory gases oxygen and carbon dioxide.Granulocytes and monocytes are cells that can exit from blood vessels and migrate among the cells of many tissues. These two cell types play key roles in inflammation and phagocytosis. Platelets are very small, anucleate cells that contain molecules required for hemostasis. In addition, platelets provide hemostasis through their abilities to adhere, aggregate, and provide a surface for coagulationreactions. Lymphocytes mediate highly specific immunity against microorganisms and other sources of foreign macromolecules. B lymphocytes confer immunity through the production of specific, soluble antibodies, whereas T lymphocytes direct a large variety of immune functions, including killing cells that bear foreign molecules on their surface membranes. Despite these extreme structural and functionaldifferences among the cells of the blood, strong evidence exists that all of the blood cells are the progeny of a single type of cell: The hematopoietic stem cell (HSC). The processes involved in the production of all of the various cells of the blood from the HSCs are collectively called hematopoiesis. Hematopoiesis includes HSC self-renewal, HSC commitment to specific lineages, and maturationof lineage-committed progenitors into functional blood cells. Self-renewal may occur by symmetric HSC division, such as expansion of the HSC pool during fetal life or post-HSC transplantation. Other possible fates of HSC divisions include apoptosis or mobilization to the peripheral circulation following stress such as growth factor stimulation or depletion of marrow cells by irradiation orchemotherapy. During normal steady state conditions, HSCs reside mainly in the marrow cavity, but under certain stress conditions HSCs can migrate and colonize other organs like liver and spleen in a process termed extramedullary hematopoiesis.
Hematopoiesis begins early during embryogenesis and undergoes many changes during fetal and neonatal development. Unlike some organ systems that form in earlylife and are not continually replaced, turnover and replenishment of the hematopoietic system continue throughout life. The cells of the blood have finite lifespans, which vary depending on the cell type. In humans, granulocytes and platelets have lifespans of only a few days, whereas some lymphocytes can exist for many months. Cells are replaced as the older cells are removed and the newly formed,mature cells are added. The numbers of the various cell types in the blood are normally kept in relatively constant ranges. In particular, variations in the erythrocyte number are normally minimal, and values 30% above or below the norm for the population have significant health effects. Although the numbers of other blood cell types are not as constant as the number of erythrocytes, the productionof other blood cells is also highly regulated. The regulation of hematopoiesis is complex. Some regulatory factors influence overall hematopoiesis by affecting very early progenitor cells: The HSCs and/or their progeny that have not undergone commitment to a single cell lineage. Also, specific regulatory growth factors play key roles in fostering the production of cells in each lineage.Lineage-specific regulation is necessary because of the widely varying lifespans and widely varying functions of the different mature blood cell types.
This chapter presents an overview of human hematopoiesis. However, many experiments on hematopoiesis have been done with mice, and many of the conclusions presented here are based on those experiments. All cell lineages that compose the blood are...