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Differentiation, in Vitro and in Vivo

CELL DIFFERENTIATION, or cellular differentiation, is the process by which the cells of a multicellular organism develop the specialized abilities required by each of the organism's several structures. In the context of stem cell biology, it should be noted that the two defining characteristics of stem cells are the ability to pass through several mitotic cycles without differentiating—a property known as self—renewal—and the ability to differentiate into any mature cell type. This property is known as totipotency. There are some cells that can differentiate into many, but not all, mature cell types. Although these cells are not totipotent, they are occasionally considered to be stem cells and are called multipotent.

Cell differentiation occurs via the differential expression of cellular genes, so that the cellular proteins formed vary from cell type to cell type. It may take place in vivo, or in the body of the living organism, or be induced in vitro, in the laboratory. Differentiation is an essential stage in the development of an organism and is necessary for maintaining its particular form and identity.

Cell differentiation is closely regulated by cellular signaling substances called cytokines and by the extracellular matrix that surrounds the cell. It affects some disease states—some genes that were known to inhibit the growth of tumors have been found to act by promoting the differentiation of tumor cells, inhibiting their spread. In others, it is affected itself; for example, infection by the HIV virus has been found to induce differentiation in some cells. Certain factors, such as the products of oncogenes, have been found to reverse differentiation—in this way, a differentiated adult cell may be reverted to pluripotency. However, because this reversal of differentiation involves the use of oncogenes, which can transform normal cells into malignant tumor cells, its application is likely to be restricted.

Cell differentiation requires the cell to turn through the cell cycle several times, as the promotion of the expression of certain genes and the simultaneous suppression of others is a molecu—larly complex process. Certain cells remain undif—ferentiated into adulthood and are called adult stem cells. Reservoirs of these cells exist in the bone marrow, and the cells are present in smaller quantities in the brain, muscle, and heart.

Cell Differentiation in Vivo

Differentiation is the third phase of embryonic development, the first two being growth and morphogenesis. It results in the formation of tissues and organ systems that are capable of performing certain specialized functions. In the context of embryogenesis, most major differentiation processes begin at the stage of gastrulation; this is the process in which cells migrate to the interior of the blastula and subsequently give rise to two or three germ layers from which the body's various organs develop; the embryo at this stage is known as a gastrula.

The embryo's organs and tissues differentiate rapidly in the fourth to eighth weeks and are at risk for congenital anomalies if exposed to teratogens during this period (teratogens are agents—chemical, physical, or biological—that can increase the incidence of such anomalies. Notorious examples are X—ray radiation, thalido—mide, and the rubella virus).

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