M2 Notes

Topics: Bone marrow, Stem cell, Developmental biology Pages: 5 (1528 words) Published: October 28, 2014
MODULE TWO

M2L1
Slide 1
The process that generates all of our blood cells is called hematopoesis. This multistep process takes place mostly in the bone marrow. Hematopoiesis actually starts in embryonic development at a different site called the yolk sac, but at this early stage, only a few types of cells are generated. The process moves to other places, such as the fetal liver, but at birth, most hematopoiesis occurs in the bone marrow. At any given time, there is a hierarchy of cells in the bone marrow, each stage or level characterized by the potential to differentiate or to expand in large numbers by cell division. The proliferation potential decreases as the cell proceeds from a more primitive or undifferentiated state to a more differentiated state. Slide 2

For such a complex process, it is amazing that the number of blood cells for each type remains the same under steady-state conditions. Feedback mechanisms are in place to ensure that just the right number of cells for each type is generated to meet the individual’s needs for oxygen delivery, immune defense, and maintenance of vascular integrity. Under certain conditions, as in hemorrhage or infection, just the right type of blood cell is expanded to compensate for the loss or to meet the demands of the individual. Red blood cell proliferation and differentiation increase with acute blood loss. White blood cells increase in number during acute infection. In the absence of serious pathology, the blood system returns to its basal state once the needs of the individual are met. Blood system homeostasis is ensured by an adequate supply of bone marrow stem cells, which remain small in number, but are able to meet the demands through the process of self-renewal. Part of the stem cell progeny commits to a specific lineage of blood cells, after which they expand and differentiate on a particular pathway. When cells emerge from the bone marrow and go into circulation and in tissues to carry out their functions, they are said to be terminally differentiated. Slide 3

You can see that less than 5% of cells in the bone marrow represent the earlier stages of stem and progenitor cells. The stem cell population, which replenishes all lineages of blood cells, is a small and quiescent population. Even the progenitor cell population, which has gone into one of the major lineages, remains small. Once the cell has committed and gone down a specific pathway, this cell has the ability to expand into large populations of the same type of differentiated cell. Stem cells are able to self-renew. A few of them may give rise to more stem cells, but many of them are capable of asymmetric cell division. This means that one daughter cell remains a stem cell while the other daughter cell becomes a progenitor cell. That way, you maintain the small population of stem cells, which at any given moment, you and I each have about 20,000 stem cells, while you also replenish the pool of cells that are differentiating. The developmental potential not surprisingly decreases as you go down the hierarchy. From the pluripotent stem cell, a cell becomes unipotential once it is committed to a specific differentiation pathway. Population goes up brought about by cell division. The maturing cell population is sustained mostly by cell division. Stem cells and progenitor cells are identifiable only through functional clonal assays. In other words, you cannot distinguish them morphologically like you can the maturing cells. But clonal assays have been refined to the level of specificity that ensures that you are working with stem and progenitor cells.

Slide 4
Cells lining blood vessels, the endothelial cells, and blood cells are believed to share a common ancestor stem cell, called the hemangioblast. This type of cell is still poorly understood, and whether they exist in adults is still under investigation. Presumably hemangioblasts are abundant at an earlier time in embryonic...
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