40.9:
Regulation of Hematopoietic Stem Cells
Colony-stimulating factors or CSFs are glycoproteins that bind to receptors on hematopoietic stem cells or HSCs to regulate their growth and differentiation.
CSFs circulate in the blood and bone marrow as soluble factors. Stromal cells also secrete membrane-bound CSFs called stem cell factors to keep quiescent HSCs inactive and maintain the stem cell pool.
As active HSCs divide and differentiate into committed progenitors, CSFs stimulate the progenitors to proliferate and differentiate to form colonies of specific blood cell types.
Upon microbial infection, CSFs induce progenitors to produce immune cells that are released into the bloodstream to attack the invading microbes.
In the absence of CSFs, the immune cells undergo apoptosis, preventing the cancerous growth of blood cells.
40.9:
Regulation of Hematopoietic Stem Cells
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or activate autoimmune responses. Thus, hematopoiesis needs to be a tightly regulated process.
Regulation of hematopoiesis helps determine whether the HSCs stay quiescent or undergo any other fate such as self-renewal, differentiation, or apoptosis. Several soluble or membrane-bound factors such as cytokines or colony-stimulating factors (CSFs) regulate hematopoiesis. For example, stem cell factors or steel produced by the bone marrow stroma make contact with c-kit receptors on quiescent HSCs, providing them with survival signals and HSC maintenance. The CSFs are inflammatory cytokines produced by fibroblasts and macrophages in response to allergies and bacterial or parasitic infections. CSFs regulate the rate of HSC proliferation and the number of cell division cycles they must undergo before differentiating into progenitor cells. This ensures the human body possesses an adequate reserve of stem cells to maintain all blood cell types. CSFs also induce the progenitors to commit to lineage-specific blood and immune cells and perform their functions. They assist with rapid differentiation into specific immune cells and elicit an immediate immune response until the infection is cleared. In the absence of CSFs, HSCs undergo apoptosis.
Suggested Reading
- Opferman, J. T. (2008). Apoptosis in the development of the immune system. Cell Death & Differentiation, 15(2), 234-242.
- Morrison, S. J., Uchida, N., & Weissman, I. L. (1995). The biology of hematopoietic stem cells. Annual review of cell and developmental biology, 11(1), 35-71.
- Zhang, C. C., & Lodish, H. F. (2008). Cytokines regulating hematopoietic stem cell function. Current opinion in hematology, 15(4), 307.
- King, K. Y., & Goodell, M. A. (2011). Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response. Nature Reviews Immunology, 11(10), 685-692.
- Rieger, M. A., & Schroeder, T. (2012). Hematopoiesis. Cold Spring Harbor perspectives in biology, 4(12), a008250.