contrast to a unipotent cell, which differentiates into a single cell type, a hematopoietic stem cell is multipotent, or pluripo-tent, able to differentiate in various ways and thereby generate erythrocytes, granulocytes, monocytes, mast cells, lymphocytes, and megakaryocytes. These stem cells are few, normally fewer than one HSC per 5 X 104 cells in the bone marrow.
The study of hematopoietic stem cells is difficult both because of their scarcity and because they are hard to grow in vitro. As a result, little is known about how their proliferation and differentiation are regulated. By virtue of their capacity for self-renewal, hematopoietic stem cells are maintained at stable levels throughout adult life; however, when there is an increased demand for hematopoiesis, HSCs display an enormous proliferative capacity. This can be demonstrated in mice whose hematopoietic systems have been completely destroyed by a lethal dose of x-rays (950 rads; one rad represents the absorption by an irradiated target of an amount of radiation corresponding to 100 ergs/gram of target). Such irradiated mice will die within 10 days unless they are infused with normal bone-marrow cells from a syngeneic (genetically identical) mouse. Although a normal mouse has 3 X 108 bone-marrow cells, infusion of only 104-105 bone-marrow cells (i.e., 0.01%-0.1% of the normal amount) from a donor is sufficient to completely restore the hematopoietic system, which demonstrates the enormous proliferative and differ -entiative capacity of the stem cells.
Early in hematopoiesis, a multipotent stem cell differentiates along one of two pathways, giving rise to either a common lymphoid progenitor cell or a common myeloid progenitor cell (Figure 2-1). The types and amounts of growth factors in the microenvironment of a particular stem cell or progenitor cell control its differentiation. During the development of the lymphoid and myeloid lineages, stem cells differentiate into progenitor cells, which have lost the
Hematopoietic stem cell
Hematopoietic stem cell
Hematopoiesis. Self-renewing hematopoietic stem cells give rise to lymphoid and myeloid progenitors. All lym-phoid cells descend from lymphoid progenitor cells and all cells of the myeloid lineage arise from myeloid progenitors. Note that some dendritic cells come from lymphoid progenitors, others from myeloid precursors.
capacity for self-renewal and are committed to a particular cell lineage. Common lymphoid progenitor cells give rise to B, T, and NK (natural killer) cells and some dendritic cells. Myeloid stem cells generate progenitors of red blood cells (erythro-cytes), many of the various white blood cells (neutrophils, eosinophils, basophils, monocytes, mast cells, dendritic cells), and platelets. Progenitor commitment depends on the acquisition of responsiveness to particular growth factors and cy-tokines. When the appropriate factors and cytokines are present, progenitor cells proliferate and differentiate into the corresponding cell type, either a mature erythrocyte, a particular type of leukocyte, or a platelet-generating cell (the megakaryocyte). Red and white blood cells pass into bone-marrow channels, from which they enter the circulation.
In bone marrow, hematopoietic cells grow and mature on a meshwork of stromal cells, which are nonhematopoietic cells that support the growth and differentiation of hema-topoietic cells. Stromal cells include fat cells, endothelial cells, fibroblasts, and macrophages. Stromal cells influence the differentiation of hematopoietic stem cells by providing a hematopoietic-inducing microenvironment (HIM) consisting of a cellular matrix and factors that promote growth and differentiation. Many of these hematopoietic growth factors are soluble agents that arrive at their target cells by diffusion, others are membrane-bound molecules on the surface of stromal cells that require cell-to-cell contact between the responding cells and the stromal cells. During infection, hematopoiesis is stimulated by the production of hematopoietic growth factors by activated macrophages and T cells.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.