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Hematopoiesis

Hematopoiesis is the development of blood cells from hematopoietic stem cells (HSCs).

A stem cell is any cell which can differentiate into other cell types; stem cells maintain their population via asymmetrical division -- one daughter cell differentiates (the progenitor cell), and the other daughter cell remains in the bone marrow to continue the cycle. HSCs are sensitive to chemotherapy and radiation because of their frequent divisions; this sensitivity is the main barrier to tumor eradication. Stanford researcher Dr. Weissman and his colleagues developed stem cell enrichment to separate stem cells from bone marrow tissue.

The daughter cell that will differentiate is the progenitor cell, meaning it cannot self-renew and is committed to a particular cell lineage. There are two kinds of hematopoietic progenitor cells: lymphoid progenitor cells, which give rise to B cells, T cells and NK cells; and myeloid progenitor cells, which give rise to red blood cells (erythrocytes), various other white blood cells (neutrophils, eosinophils, basophils, monocytes, mast cells and dendritic cells) and platelet-generating cells called megakaryocytes.

GeneAffected lineage
Bmi-1All lineages.
GATA-1Erythroid lineage.
GATA-2Erythroid, myeloid and lymphoid lineages.
IkarosLymphoid lineage.
PU.1Erythroid lineage maturation, myeloid lineage
(late stages) and lymhpoid lineage.
Oct-2B cell differentiation.

Most hematopoiesis occurs in the bone marrow within a hematopoiesis inducing microenvironment (HIM) that is composed of cytokine-secreting stromal cells. Stromal cells include fat, endothelial, fibroblast and macrophage cells. Some of these cytokines operate via diffusion, while others are membrane-bound to the stromal cells and require direct cell-to-cell contact. Mostly identified via knockout mice, to the left are a few of the genes critical in hematopoiesis. These genes can impact many lineages or just one.

The lifespan of a cell can range from one 1 day for neutrophils to 120 days for erythrocytes to several decades for some T cells. With most blood cells dying due to aging, hematopoiesis produces just enough cells to keep up with cell death. The average human being produces 3.7E11 daily of white blood cells alone. To prevent overpopulation or misbehavior, cells undergo apoptosis (programmed cell death) or necrosis (death in response to cell injury). In apoptosis, the cell shrivels and then is phagocytosed by a macrophage. In necrosis, the cell swells, bursts and (in a crucial difference between apoptosis and necrosis) releases its contents into the surrounding area. This release can trigger an inflammatory response in surrounding tissues.

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