Hematopoietic System Development Proteins


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 Hematopoietic System Development Proteins Background

Hematopoietic Development in the Mouse

In the mouse, primitive hematopoiesis begins at E7.5 in the extaembryonic yolk sac with blood islands where interior cells develop into blood cells and those along the periphery become endothelial cells, later forming the vascular system. At E10.5, definitive hematopoiesis begins in the aorto-gonad-mesonephrous region. While primitive hematopoiesis is a transient process resulting in production of large, nucleated erythroblasts, megakaryocytes and primitive macrophages, definitive hematopoiesis requires not only erythroid progenitors but also the hematopoietic stem cells that will reconstitute the fetus. Definitive hematopoiesis occurs primarily in the fetal liver and spleen, moving to the bone marrow after birth.

Within the hematopoietic system, there are many cell types arising from two major lineages, myeloid and lymphoid. Like in the small intestine, the cell fate decisions of hematopoietic cells are influenced by transcription factors. Again, we start with stem cells, which are not only able to self-renew but also have the potential to differentiate into various progenitor cells and eventually mature into specifically differentiated cells types. Renewal of the stem cells is governed by the NotcM, Ikaros, HoxB4 and GATA-2 transcriptional regulators. For differentiation to a common myeloid progenitor, PU.1 and GATA-1 must be expressed whereas the common lymphoid progenitor requires expression of PU.1, GATA-3, and Ikaros. It is not only expression of these factors that governs differentiation but also the levels at which they are expressed, as PU.1 is known to exhibit concentration-dependent effects on differentiation.

The common myeloid progenitor will give rise to monocytes, neutrophils, eoisinophils, mast cells, red cells, and megakaryocytes. Monocytes will further differentiate into macrophages, and megakaryocytes will give rise to platelets. The common lymphoid progenitor will give rise to B- and T-cells; both of which function in immunity. T-cells work in cell-mediated immunity and activate B-cells, which produce antibodies to fight infection. With the expression of cell-surface markers varying at each stage of differentiation and the advent of fluorescence activated cell sorting (FACS) techniques, study of the individual cell types has been made much less complicated; however, many additional transcription factors may be involved at any step of the process from hematopoietic stem cell to fully differentiated cell.