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19.4Cell Differentiation and Stem Cells

During the developmental process, one fertilized egg finally becomes cells with various functions, such as muscle cells, neurons, and epithelial cells, through cleavage, specification and morphogenetic movement. This phenomenon is called cell differentiation.

Embryonic cells in the early developmental stage have the potential to become various cell types. These cells, which have not yet undergone differentiation, are referred to as undifferentiated cells. However, as development progresses, most cells are differentiated into cells with particular functions. Each differentiated cell type shows a different gene expression pattern and level (Figure 19-11). In other words, in differentiated cells, the expression of certain genes necessary to fulfill their cellular functions is enhanced, whereas the expression of unnecessary genes is suppressed. Although cells divide and differentiate during development, their genome volume (genetic information volume) remains unchanged.

In differentiated cells, the suppression of unnecessary genes is elicited through chemical modification of the genes themselves (or of proteins that bind to them) or through the binding of special proteins to them. Such suppression may be temporary or semi-permanent (see Selection 4 of Chapter 10). If the suppression is unlocked, thus allowing gene expression, the cells regain the potential to be transformed into other cells.

Cells that retain the ability to differentiate into many cell types exist in various tissues of the human body. These are known as somatic stem cells, and are believed to be involved in the repair of damaged tissues. Attempts have recently been made to collect, grow, and differentiate these cells in order to artificially create tissues and organs. The aim is to create tissues and organs using stem cells obtained from patients and implant them back into the body. Somatic stem cells are thought to differentiate only in a certain direction; thus, the tissues and organs into which they can differentiate are limited. In mammals, cell differentiation occurs after the blastocyst stage in the early stages of development. During this stage, the inner cell mass has pluripotent differentiation ability, which means that it can differentiate into all types of tissues. Attempts are also being made to create tissues and organs using embryonic stem cells (ES cells; see Chapter 24), which themselves are produced from this inner cell mass. Because ES cells can differentiate into various tissues, they can be used for various applications. However, this raises ethical issues because ES cells can only be obtained by destroying embryos. Furthermore, immunological rejection is a problem because ES cells are not the patient’s own cell but cells derived from other people.

Figure 19-11 Cell differentiation

A model showing changes in the gene expression pattern during cell differentiation. Through cleavage and specification, embryonic cells differentiate into those with various functions. During this process, the new cells come to exhibit gene expression patterns different from the original cell. The expression patterns of genes seen in the differentiated cells differ by cell type. Although differentiated cells have the same gene set (genome) as the fertilized egg, the gene expression patterns and levels differ.

In recent years, induced pluripotent stem cells (iPS cells ) have been developed. As described earlier, gene expression is regulated in normal somatic cells (only the required genes are expressed, whereas the unnecessary genes are inhibited). With iPS cells, however, gene expression is artificially deregulated to create multifunctional stem cells. iPS cells are prepared by returning the differentiated somatic cells of the skin of the patient to the undifferentiated state by introducing four types of transcription factors and maintaining this undifferentiated state. Like ES cells, iPS cells are able to differentiate into various tissues; however, unlike ES cells, they can be generated without destroying embryos and are not accompanied by immunological rejection because they can be generated from the patient’s own cells. Since they are expected to resolve the various problems associated with ES cells, research on iPS cells are presently being conducted on a large scale.

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