Multipotent Somatic Stem Cells Give Rise to Both Stem Cells and Differentiating Cells
The most common type of stem cells in adult metazoans, multipotent somatic stem cells, give rise to the specialized cells composing body tissues. Multipotent somatic stem cells have three key properties (Figure 21-10):
They can give rise to multiple types of differentiated cells; that is, they are multipotent. In this sense, they are different from progenitor cells (also called precursor cells), which generally give rise to only a single type of differentiated cell. A stem cell has the capability of generating a number of different cell types, but not all cell types; that is, it is not pluripotent like an ES cell. For instance, a multipotent blood stem cell will form more of itself plus multiple types of blood cells, but never a skin or a liver cell.
They are stem cells in that they are undifferentiated; in general, they do not express proteins characteristic of the differentiated cell types formed by their descendants.
The number of stem cells of a particular type generally increases during embryonic development and then remains relatively constant over the remainder of an individual’s lifetime. In that sense, stem cells are often said to be immortal, although no single stem cell survives for the life of the animal. Indeed, when pushed to divide more frequently than normal by chronic tissue injury, repeated rounds of chemotherapy, or genetic defects that impair genomic integrity, stem cells consistently exhibit a finite replicative capacity.
FIGURE 21-10 The pathway from stem cells to lineage-restricted progenitors to differentiated cells. On average, during each division of a multipotent somatic stem cell, at least one of the daughter cells becomes a stem cell like the parent cell. Stem cells thus undergo self-renewal divisions such that the number of stem cells of a particular type stays constant or increases during the organism’s lifetime. Other daughter cells, termed transient amplifying cells, divide rapidly and undergo limited numbers of self-renewal divisions, but ultimately produce lineage-restricted progenitor cells. These cells cannot undergo self-renewal divisions, but can divide and produce differentiated cells of a particular type.
The two critical properties of stem cells that together distinguish them from all other cells are the ability to reproduce themselves during many cell divisions (self-renewal) and the ability to generate progeny of more restricted potential. Many types of stem cells in the adult body divide infrequently; they are kept “in reserve” in case certain types of differentiated cells are required. In contrast, their non-stem-cell daughters frequently undergo many rapid rounds of cell division. Such cells, often called transient amplifying cells (see Figure 21-10), can have limited self-renewal capabilities, but eventually their many progeny form lineage-restricted progenitor cells. These cells, in turn, can divide and generate very specific types of terminally differentiated cells.
Stem cells can exhibit several patterns of cell division. Some types of stem cells always divide asymmetrically to generate one copy of the parent cell and one daughter stem cell that has more restricted capabilities, such as dividing for a limited time or giving rise to fewer types of progeny than the parent stem cell (Figure 21-11a). This type of stem-cell division is commonly found in invertebrates such as Drosophila, discussed below.
FIGURE 21-11 Patterns of stem-cell differentiation. Different patterns of stem-cell division produce different proportions of stem cells (red) and differentiating cells (green). Stem-cell divisions must meet three objectives: they must maintain the stem-cell population, they must sometimes increase the number of stem cells, and at the right time, they must produce cells that go on to differentiate. (a) Stem cells can undergo asymmetric divisions, producing one stem cell and one differentiating cell. This pattern does not increase the population of stem cells. (b) Some stem cells can divide symmetrically to increase their population, which may be useful in normal development or during recovery from injury, at the same time that others in the same population can be dividing asymmetrically as in (a). (c) Some stem cells may divide as in (b) while at the same time other stem cells produce two differentiating progeny. See S. J. Morrison and J. Kimble, 2006, Nature 441:1068–1074.
Other patterns of stem-cell division, commonly found in vertebrates, allow the number of stem cells or differentiated cells to increase or decrease according to the needs of the animal (Figure 21-11b, c). Hormones released by adjacent cells frequently regulate these patterns of stem-cell division. For example, a stem cell may divide symmetrically to yield two daughters that undergo different fates: depending on external signals sent by other cells, one may remain a stem cell and the other may generate differentiated progeny. As we will see in greater detail shortly, this happens in the small intestine: often one of the daughters remains a stem cell identical to its parent while the other daughter divides rapidly and generates four types of differentiated intestinal cells. Other stem-cell divisions are symmetric, producing two stem cells and increasing the number of stem cells of a particular type; this pattern of stem-cell division is common during development. Thus mitotic divisions of stem cells can either enlarge the population of stem cells or maintain a stem-cell population while steadily producing a stream of differentiating cells.