Introduction | Stem Cell Basics | Plasticity | Stem Cell Niches | Induced Pluripotent Stem Cells | iPS-Derived MSCs | Additional Reading
Totipotency
For most multicellular organisms, the only totipotent stem cell is the fertilized egg – commonly referred to as the zygote. “Totipotent” refers to the ability to differentiate into any cell type as well as support structures of the developing embryo, including the placenta. During embryological development, the zygote undergoes a series of cell divisions resulting in a cluster of cells known as blastomeres. The blastomeres ultimately arrange themselves to form the blastocyst, which consists of a hollow sphere of blastomeres (known as the trophectoderm) with a crescent-shaped cluster of cells attached to the inner wall of the sphere known as the inner cell mass. The cells in the inner cell mass will go on to form the organism. Having lost their totipotency, these cells are now known as “pluripotent.”
Pluripotency
The inner cell mass stem cell, also known as an “embryonic stem cell”, possesses the ability to differentiate into all three germ layers of the developing organism. This level of plasticity is known as “pluripotency.” When the number of cells in the inner cell mass have reached a sufficient number, the cells rearrange their location and differentiate into developmental germ layers (the endoderm, ectoderm, and mesoderm), a process known as gastrulation. These developmental layers will go on to generate organs, structures, and connective tissue of the fetal organism. Embryonic stem cell cultures are generated from dissociated inner cell mass cells. In the laboratory, adult cells can be induced to a pluripotent state which behave similarly to embryonic stem cells (see induced pluripotent stem cells).
Multipotency
Upon gastrulation, inner cell mass cells have committed to one of the three germ layers. These germ layers are composed of stem cells that are further restricted in their plasticity, with stem cells from different germ layers restricted to the development of specific categories of tissue. As such, the stem cells of each germ layer give rise to the following adult tissues:
- The Ectoderm differentiates into the epidermis including the hair and nails, components of the nervous system, epithelia of the eye, nose and ear, as well as other epithelial and neuronal tissues.
- The Mesoderm gives rise to the skeleton, muscle, connective tissues, circulatory system, as well as the urinary and genital systems.
- The Endoderm is responsible for the formation of the cells that line the digestive, and the respiratory systems as well as the formation of liver, thyroid, and pancreatic cells.
This is, of course, not an exhaustive list!
Asymmetry
Asymmetric cell division is where a stem cell divides into two daughter cells, in which one cell remains a stem cell and one becomes a differentiated cell. There are two primary ways that this process occurs: Asymmetric cell division is where a stem cell divides into two daughter cells, in which one cell remains a stem cell and one becomes a differentiated cell. There are two primary ways that this process occurs: divisional asymmetry and environmental asymmetry.
Divisional Asymmetry
In this situation, the division of these cells results in inherently different daughter cells in which one remains a replaced stem cell and the other a differentiated cell. Because this is an inherent property of the daughter cell, environmental stimuli are not necessarily required to ensure asymmetric cell division. This results in a 1:1 relationship between stem cells to differentiated cells.
Environmental Asymmetry
Once again, this form of cell division can result in the replacement of a stem cell and creation of a differentiated cell, but depending on how the division occurs it can also result in the production of two daughter stem cells. If the resultant daughter cells are exposed to equivalent external conditions, they both become stem cells but if they are exposed to contrasting conditions, one daughter cell becomes destined for differentiation. In the example above, the external microenvironment could be attachment to (or detachment from) the basal lamina. This is achieved by division along (or perpendicular to) the plane of the basal lamina. This example of environmental asymmetric cell division is very common in biology.
Transit Amplification
Adult stem cells will divide slowly and for the duration of the lifetime of the organism. Just before the process of differentiation, many stem cells will undergo a transient proliferative burst. At this point the stem cell loses its proliferative immortality but has the capacity to divide very rapidly for a limited number of population doublings. This process increases the number of cells capable of differentiation and also relaxes proliferative stress on the stem cell pool. This acts as a safeguard to prevent biologically immortal cells from uncontrolled division in an adult organism. This process is referred to as transit amplification.
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