Analysis of Hematopoietic Phenotypes in Knockout Mouse Models
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The hematopoietic and vascular system of the developing embryo share a common mesodermal precursor, the hemangioblast (1 –3 ). The primitive hematopoietic system arises in the extraembryonic blood islands of the yolk sac and the aorta-gonad-mesonephros (AGM) region of the embryo. Multipotent hematopoietic stem cells from these primary sites then migrate through the developing vascular system to colonize the fetal liver. Late in gestation, fetal liver-derived stem and progenitor cells seed the developing bone marrow, spleen, and thymus. In the adult, the hematopoietic system comprises an hierarchically ordered, concatenated series of stem and progenitor cell compartments of progressively restricted potentiality and proliferative capacity (4 ) (see Fig. 1 ). These processes are precisely regulated by the complex interplay of cytokines, accessory cells, stromal cells, and matrix. This involves the coordinated expression of many genes that directly or indirectly govern hematopoietic stem and progenitor cell maintenance, maturation, lineage commitment, and differentiation; cell migration, mobilization, and sequestration; and mature blood cell function (5 –7 ).
Fig. 1. Schematic representation of the hierarchical organization of the hematopoietic system, surrogate stem, and progenitor cell assays (34 –36 ), and the level of expression of hematopoietic lineage antigens during lymphoid (33 ), myeloid, and erythroid cell maturation and differentiation. Abbreviations: LTRA-stem cells with long-term reconstituting ability in vivo; CAFC-cobblestone area-forming cell; LTCIC- long-term culture-initiating cell; CFU-S12 -colony-forming unit-spleen measured 12 d posttransplantation; HPP-CFC1 and −2 -high-proliferative potential colony-forming cells stimulated by IL1α + IL3 + CSF-1 and IL3 + CSF-1 respectively; CFU-GEMM-colony-forming unit-granulocyte/ erythrocyte/macrophage/megakaryocyte; CFU-GM-colony-forming unit-granulo-cyte/macrophage; BFU-E-burst-forming unit-erythroid; LPP-CFC-low proliferative potential colony-forming cell.
