Читать книгу The SAGE Encyclopedia of Stem Cell Research - Группа авторов - Страница 144

HSCs have been shown to develop from embryonic mesodermal hemangioblast cells. Once the precursors have been specified from the mesoderm, they divide to form a pool of functional HSCs. This pool moves through embryonic niches, such as the yolk sac, placenta, and fetal liver, which provide signals for their establishment and self-renewal ability. The HSCs move to occupy the bone marrow at birth and a steady state is established. Most HSCs are quiescent (in the G₀ phase) and division is tightly controlled to maintain the pool as well as the differentiated blood cells. When differentiation is required, cell division is asymmetric, giving rise to a long-term HSC daughter cell, which retains self-renewal capacity and a short-term HSC daughter cell/progenitor with limited self-renewal capacity. The progenitors may follow the erythroid (producing erythrocytes), lymphoid (producing B cells and T cells) or myeloid lineages (producing granulocytes, megakaryocytes, and macrophages).

Commitment to a specific lineage and further maturation has been found to be influenced by cytokines (cell-signaling proteins) and growth factors. The cytokines include those in the common beta chain, common gamma chain, and interleukin-6 families. The growth factors involved include epidermal growth factor, fibroblast growth factor, growth differentiation factor, insulin-like growth factor, platelet derived growth factor, and vascular endothelial growth factor. In addition, activins, bone morphogenetic proteins, and hedgehog molecules also determine the fate of the HSCs. These factors act in various ways, primarily controlling the expression of certain genes.

The erythroid, lymphoid, and myeloid lineages can be traced because of the presence of specific markers. Human HSCs can be identified by high levels of CD54 expression. Lymphoid cells show enhanced expression of MS4A1/CD20 and CD4 in cells differentiating into B cells and T cells, respectively. Antibodies are also available to detect the differentiation of the myeloid cells.