In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a single zygote to a complex system of tissues and cell types. Differentiation is a common process in adults as well: adult stem cells divide and create fully-differentiated daughter cells during tissue repair and during normal cell turnover. Cell differentiation causes its size, shape, polarity, metabolic activity, and responsiveness to signals to change dramatically. These changes are largely due to highly-controlled modifications in gene expression. With a few exceptions, cellular differentiation almost never involves a change in the DNA sequence itself. Thus, different cells can have very different physical characteristics despite having the same genome.
A cell that is able to differentiate into many cell types is known as pluripotent. These cells are called stem cells in animals and meristematic cells in higher plants. A cell that is able to differentiate into all cell types is known as totipotent. In mammals, only the zygote and early embryonic cells are totipotent, while in plants, many differentiated cells can become totipotent with simple laboratory techniques. In cytopathology the level of cellular differentiation is used as a measure of cancer progression. "Grade" is a marker of how differentiated a cell in a tumor is.
Germ line cells are any line of cells that give rise to gametes—eggs and sperm—and thus are continuous through the generations. Stem cells, on the other hand, have the ability to divide for indefinite periods and to give rise to specialized cells. They are best described in the context of normal human development.
Development begins when a sperm fertilizes an egg and creates a single cell that has the potential to form an entire organism. In the first hours after fertilization, this cell divides into identical cells. In humans, approximately four days after fertilization and after several cycles of cell division, these cells begin to specialize, forming a hollow sphere of cells, called a blastocyst. The blastocyst has an outer layer of cells, and inside this hollow sphere, there is a cluster of cells called the inner cell mass. The cells of the inner cell mass will go on to form virtually all of the tissues of the human body. Although the cells of the inner cell mass can form virtually every type of cell found in the human body, they cannot form an organism. These cells are referred to as pluripotent.
Some believe dedifferentiation is an aberration of the normal development cycle that results in cancer, whereas others believe it to be a natural part of the immune response lost by humans at some point as a result of evolution.
A small molecule dubbed reversine, a purine analog, has been discovered that has proven to induce dedifferentiation in myotubes. These dedifferentiated cells were then able to redifferentiate into osteoblasts and adipocytes.
A few evolutionarily conserved types of molecular processes are often involved in the cellular mechanisms that control these switches. The major types of molecular processes that control cellular differentiation involve cell signaling. Many of the signal molecules that convey information from cell to cell during the control of cellular differentiation are called growth factors. Although the details of specific signal transduction pathways vary, these pathways often share the following general steps. A ligand produced by one cell binds to a receptor in the extracellular region of another cell, inducing a conformational change in the receptor. The shape of the cytoplasmic domain of the receptor changes, and the receptor acquires enzymatic activity. The receptor then catalyzes reactions that phosphorylate other proteins, activating them. A cascade of phosphorylation reactions eventually activates a dormant transcription factor or cytoskeletal protein, thus contributing to the differentiation process in the target cell . Cells and tissues can vary in competence, their ability to respond to external signals .
Induction refers to cascades of signaling events, during which a cell or tissue signals to another cell or tissue to influence its developmental fate . Yamamoto and Jeffery investigated the role of the lens in eye formation in cave- and surface-dwelling fish, a striking example of induction. Through reciprocal transplants, Yamamoto and Jeffery found that the lens vesicle of surface fish can induce other parts of the eye to develop in cave- and surface-dwelling fish, while the lens vesicle of the cave-dwelling fish cannot.
Other important mechanisms fall under the category of asymmetric cell divisions, divisions which give rise to daughter cells with distinct developmental fates. Asymmetric cell divisions can occur because of segregation of cytoplasmic determinants or because of signaling . In the former mechanism, distinct daughter cells are created during cytokinesis because of an uneven distribution of regulatory molecules in the parent cell; the distinct cytoplasm that each daughter cell inherits results in a distinct pattern of differentiation for each daughter cell. A well-studied example of pattern formation by asymmetric divisions is body axis patterning in Drosophila. RNA molecules are an important type of intracellular differentiation control signal. The molecular and genetic basis of asymmetric cell divisions has also been studied in green algae of the genus Volvox, a model system for studying how unicellular organisms can evolve into multicellular organisms . In Volvox carteri, the 16 cells in the anterior hemisphere of a 32-celled embryo divide asymmetrically, each producing one large and one small daughter cell. The size of the cell at the end of all cell divisions determines whether it will become a specialized germ or somatic cell .
"Transduction of Human Trophoblastic Cells by Replication-Deficient Recombinant Viral Vectors: Promoting Cellular Differentiation Affects Virus Entry".(Brief Article)(Statistical Data Included)
Aug 17, 1998; Parry, S.; Holder, J.; Halterman, M. W.; Weitzman, M.D.; Davis, A.R.; Federoff, H.; Strauss, J.F. "Transduction of Human...
Recombinant Viral Vectors "Transduction of Human Trophoblastic Cells by Replication-Deficient Recombinant Viral Vectors: Promoting Cellular Differentiation Affects Virus Entry."
Aug 10, 1998; Parry, S.; Holder, J.; Halterman, M.W.; Weitzman, M.D.; Davis, A.R.; Federoff, H.; Strauss, J.F. American Journal of Pathology,...
Establishment and maintenance of a heterochromatin domain. (Research Articles).(cellular differentiation research)
Sep 27, 2002; In eukaryotes, the organization of chromatin into higher-order structures governs diverse chromosomal processes. Besides creating...