Understanding Conditional and Autonomous Specification during Cell Differentiation

Stem cells have received a great deal of public attention over the past few years due both to their interesting biological characteristics and their therapeutic potential. What makes stem cells unique over other cells found in the human body is that they are capable of renewing themselves for long periods and, importantly, they can be induced to become specialized cell types such as muscle cells or insulin-producing pancreatic cells. To better realize the therapeutic potential of stem cells, much of the current scientific research has been aimed at understanding how cells differentiate.

Cell differentiation is the process by which unspecialized cells give rise to specialized cell types and involves changes in a cell’s size, shape, gene expression, biochemistry, and function. Differentiation occurs during embryonic development and in adults during tissue repair and normal cell turnover. Scientists have just begun to understand the internal and external signals that regulate cell differentiation. Specialized cell types are defined by their particular pattern of gene expression and differentiation involves the turning on and turning off of particular genes. In addition, external signals including physical contact with neighboring cells and exposure to chemicals secreted by other cells within the microenvironment also regulate cell differentiation.

Through the study of embryogenesis, the process by which an embryo is formed and develops, two types of cell differentiation have been identified. The first type of differentiation is called conditional specification. Initially, each cell has the capacity to become many different cell types. However, interactions of a cell with surrounding cells and the environment can restrict the fate of that cell. This mode of differentiation is called conditional specification because how a cell becomes specialized is dependent upon the conditions in which the cell finds itself. For example, if a cell is removed from an early embryo that uses conditional specification, the remaining embryonic cells will alter their differentiation pathway as to compensate for the loss of that cell type and function. Removed from the environment of the embryo, the isolated cell is now free to give rise to a wide variety of cell types, even those not normally part of the embryo. Conditional specification has been observed in all vertebrates and few invertebrates.

The second type of cell differentiation is called autonomous specification. Autonomous specification occurs independently of interactions with the surrounding environment and is dependent on the segregation of certain factors (proteins or messenger RNAs) responsible for cell specialization within the cytoplasm of different cells following division. This process of differentiation gives rise to a pattern of embryonic development referred to as mosaic development, since the embryo appears to be constructed like a tile mosaic of independent self-differentiating parts. In this case, if a particular cell is removed from an embryo early during development, the isolated cell will produce the same cell types that it would have normally made if it were still part of the embryo. In addition, the cell types normally derived from that isolated cell will be missing in the embryo from which that cell was taken. Autonomous specification is a characteristic of most invertebrates.

Continued study of both conditional and autonomous specification will likely result in a greater understanding of those genes and molecules responsible for controlling cell differentiation. For example, identifying those signals capable of directing stem cells to differentiate into specialized cell types could lead to ways of generating surrogate cells and tissues for the treatment aliments such as Parkinson’s disease, spinal cord injury, heart disease, diabetes. In addition, knowing how certain genes involved in differentiation are turned on and turned off may provide information on how diseases associated with abnormal cell differentiation, such as cancer, arise and how to treat such diseases effectively.


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