cell differentiation, process by which an immature cell develops into a specialized cell type with a distinct structure and function.

Cell differentiation is a crucial part of development in multicellular organisms, since it results in cells with unique characteristics—such as muscle cells, neurons, or red blood cells—and thereby enables cells to form tissues and organs with specific functions. It also serves a vital role in the regeneration of tissues, namely skin and blood, which require constant repair and renewal. In general once a cell is differentiated, it usually is unable to revert to an undifferentiated state, although certain processes, such as the generation of induced pluripotent stem cells, can reverse cell specialization.

Stages of cell differentiation

The stages of differentiation include a stem cell stage, a progenitor cell stage (also known as the transit-amplifying cell stage), and a terminally differentiated cell stage. In the stem cell stage, asymmetric stem cell division, with few exceptions, typically yields one daughter cell that rejoins the stem cell population and a second daughter cell that becomes targeted for differentiation and thus becomes a progenitor cell. In the progenitor cell stage, cell division produces additional daughter cells that are partly differentiated, becoming increasingly specialized with each round of cell division. Progenitor cells are restricted to a limited number of divisions before committing to a particular cell type. Terminal differentiation, in which cells become defined by specific properties, marks the end of cell division.

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cell: Cell differentiation

Factors influencing differentiation

Differentiation is influenced by various factors, particularly gene expression. Molecules that become activated by environmental signals, such as growth factors or hormones, or by signals from neighboring cells interact with designated receptors on the stem cell surface. These interactions lead to the activation or repression of transcription factors that dictate gene expression. Changes in the expression of specific genes ultimately determine cell specialization. Epigenetic changes, which are modifications to DNA (e.g., methylation), further influence gene expression. Physical conditions, such as osmotic pressure, may also be influential.

Examples and role in disease

Embryonic development is a prime example of cell differentiation. During this period embryonic stem cells differentiate into the three germ layers: the ectoderm, the mesoderm, and the endoderm. Cells in the ectoderm differentiate to form tissues such as the skin, brain, and nerves. Cells in the mesoderm, meanwhile, differentiate into cell types that form blood vessels, bones, muscles, and certain other tissues. In the endoderm, cells differentiate to form various tissues, including the digestive tract and lungs. Another example of cell differentiation is blood cell formation, or hematopoiesis. In this process, stem cells in the bone marrow differentiate into red blood cells, white blood cells, and platelets.

Aberrant cell differentiation is involved in certain diseases. In tumor formation and cancer, for instance, the uncontrolled growth of cells is often attributed to failures in the differentiation process. Problems in cell maturation and specialization can also result in neurodevelopmental disorders and congenital disorders, such as congenital heart disease. The failure of stem cells to differentiate appropriately, which can occur as stem cells age, may result in impaired tissue regeneration.