Hematopoietic stem cells and progenitor cells: their role in normal blood formation 1

Published on March 5, 2014   28 min
0:00
I'm Malcolm Moore. And I'm a professor of cell biology at Memorial Sloan-Kettering Cancer Center in New York. And I would like to talk to you today about hematopoietic stem cells and progenitor cells and their role in normal blood formation.
0:17
What are stem cells? Well, the simple definition is cells that replicate and self-regenerate. This is called self-renewal. And they can do so extensively, only limited by a progressive shortening of the ends of the chromosomes. This is called telomeric shorting. And when they lose a sufficient amount of DNA at the ends of these chromosomes, they undergo death by a DNA damage response. So this is called the Hayflick limit. The shortening of telomeres can be prevented by telomerase enzyme expression. And many stem cells, there are different types, actually produce telomerase. Embryonic stem cells, those that are identified as capable of generating embryos, undergo symmetric self-renewal. And they give rise to all the specialized tissues of the body. Symmetric self-renewal is basically where the stem cell gives rise to two daughter stem cells. Somatic stem cells, that is to say stem cells of the adult, include hematopoietic stem cells, a rare sub-population of tissue-specific, relatively undifferentiated cells that undergo asymmetric division. They're capable of extensive self-renewal. And they can give rise not only to the different types of blood cell, the red cells, platelets, and white blood cells, but also the cells of the immune system and other sub-populations, such as dendritic cells. This definition was established for a hematopoietic stem cells 45 years ago and is still valid today.
2:02
As I mentioned, stem cells in the bone marrow are a rare population of cells, only about 0.01% to 0.001% of all cells. And as shown in this model, we can see that in the adult, symmetric division means that basically stem cells replace themselves at each division. This is a value of 0.5, which would be the method of determining whether or not the stem cell was, on average, totally asymmetric. But clearly, in the embryo, stem cells must expand to match growth. And in umbilical cord blood, that is the blood that we find in the cord at the time of birth, is a very rich source of stem cells and is used for many studies on hematopoiesis and hematopoietic stem cell function. And these represent cells that were actually derived from the fetal liver and they're in the process of moving to the bone marrow. And they have the ability not only to self-renew, but to expand. That means they undergo some symmetric divisions. And on average, this probability of symmetric versus asymmetric division is around 0.6 to 0.65. And they have these properties for, in humans, some months after birth, and some weeks after birth in the mouse. We can recognize this sub-population of feta-neonatal stem cells because of the expression of the gene SOX17. Another important point, which we will discuss in great detail later, is the importance of the niche or micro-environment in the bone marrow, which is critical as a supportive structure for maintaining the stem cells in their undifferentiated state.
4:02
Now, this model is a model that demonstrates the differentiation of the stem cells, the hierarchy, if you will, between the most primitive type of hematopoietic stem cell, which is termed the long-term reconstituting hematopoietic stem cell. It's called a long-term because if you transplant the stem cells, in a mouse, for example, one stem cell or a few stem cells will persist throughout the life of the animal, giving rise to all of the cells of the peripheral blood and the immune system. There is a short-term or even an intermediate-term stem cell that have been identified. And they simply have shorter durations of ability to self-renew and generate the mature cells. And then we have multipotential progenitor cells. These can give rise also to all the different types of blood cells. But they do not self-renew. So they're basically a transit population or a progenitor population to distinguish them from the stem cell population. And as we further progress with differentiation, we get more specialization and we recognize what are termed Common Myeloid Progenitors, CMPs, that give rise then to megakaryocytes erythroid progenitors, which then give rise to erythrocytes and platelets. Or the common myeloid progenitor gives rise to GMPs, granulocyte monocyte progenitors, giving rise to neutrophils and macrophages and also a type of dendritic cell. The common lymphoid progenitor from the multipotential progenitor gives rise, in turn, to T cells, B lymphocytes, and natural killer cell components of the immune system and also to a type of dendritic cell. This is called the Weissman model because it has been mostly proposed by Dr. Weissman. But it is not necessarily the final word.
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Hematopoietic stem cells and progenitor cells: their role in normal blood formation 1

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