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What is cell differentiation?

Why is cell differentiation important in multicellular organisms?

What are the stages of cell differentiation?

What factors influence cell differentiation?

How is cell differentiation related to disease?

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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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.

Kara Rogers

biological development, the progressive changes in size, shape, and function during the life of an organism by which its genetic potentials (genotype) are translated into functioning mature systems (phenotype). Most modern philosophical outlooks would consider that development of some kind or other characterizes all things, in both the physical and biological worlds. Such points of view go back to the very earliest days of philosophy.

Among the pre-Socratic philosophers of Greek Ionia, half a millennium before Christ, some, like Heracleitus, believed that all natural things are constantly changing. In contrast, others, of whom Democritus is perhaps the prime example, suggested that the world is made up by the changing combinations of atoms, which themselves remain unaltered, not subject to change or development. The early period of post-Renaissance European science may be regarded as dominated by this latter atomistic view, which reached its fullest development in the period between Newton’s laws of physics and Dalton’s atomic theory of chemistry in the early 19th century. This outlook was never easily reconciled with the observations of biologists, and in the last hundred years a series of discoveries in the physical sciences have combined to swing opinion back toward the Heracleitan emphasis on the importance of process and development. The atom, which seemed so unalterable to Dalton, has proved to be divisible after all, and to maintain its identity only by processes of interaction between a number of component subatomic particles, which themselves must in certain aspects be regarded as processes rather than matter. Albert Einstein’s theory of relativity showed that time and space are united in continuum, which implies that all things are involved in time; that is to say, in development.

The philosophers who charted the transition from the nondevelopmental view, for which time was an accidental and inessential element, were Henri Bergson and, in particular, Alfred North Whitehead. Karl Marx and Friedrich Engels, with their insistence on the difference between dialectical and mechanical materialism, may be regarded as other important innovators of this trend, although the generality of their philosophy was somewhat compromised by the political context in which it was placed and the rigidity with which their later followers have interpreted it.

Philosophies of the Heracleitan type, which emphasize process and development, provide much more appropriate frameworks for biology than do philosophies of the atomistic kind. Living organisms confront biologists with changes of various kinds, all of which could be regarded as in some sense developmental; however, biologists have found it convenient to distinguish the changes and to use the word development for only one of them. Biological development can be defined as the series of progressive, nonrepetitive changes that occur during the life history of an organism. The kernel of this definition is to contrast development with, on the one hand, the essentially repetitive chemical changes involved in the maintenance of the body, which constitutemetabolism,” and on the other hand, with the longer term changes, which, while nonrepetitive, involve the sequence of several or many life histories, and which constitute evolution.

As with most formal definitions, these distinctions cannot always be applied strictly to the real world. In the viruses, for instance, and even in bacteria, it is difficult to make a distinction between metabolism and development, since the metabolic activity of a virus particle consists of little more than the development of new virus particles. In certain other cases, the distinction between development and evolution becomes blurred: the concept of an individual organism with a definite life history may be very difficult to apply in plants that reproduce by vegetative division, the breaking off of a part that can grow into another complete plant. The possibilities for debate that arise in these special cases, however, do not in any way invalidate the general usefulness of the distinctions as conventionally made in biology.

greylag. Flock of Greylag geese during their winter migration at Bosque del Apache National Refugee, New Mexico. greylag goose (Anser anser)
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The scope of development

All organisms, including the very simplest, consist of two components, distinguished by a German biologist, August Weismann, at the end of the 19th century, as the “germ plasm” and the “soma.” The germ plasm consists of the essential elements, or genes, passed on from one generation to the next, and the soma consists of the body that may be produced as the organism develops. In more modern terms, Weismann’s germ plasm is identified with DNA (deoxyribonucleic acid), which carries, encoded in the complex structure of its molecule, the instructions necessary for the synthesis of the other compounds of the organism and their assembly into the appropriate structures. It is this whole collection of other compounds (proteins, fats, carbohydrates, and others) and their arrangement as a metabolically functioning organism that constitutes the soma. Biological development encompasses, therefore, all the processes concerned with implementing the instructions contained in the DNA. Those instructions can only be carried out by an appropriate executive machinery, the first phase of which is provided by the cell that carries the DNA into the next generation: in animals and plants by the fertilized egg cell; in viruses by the cell infected. In life histories that have more than a minimal degree of complexity, the executive machinery itself becomes modified as the genetic instructions are gradually put into operation, and new mechanisms of protein synthesis are brought into functional condition. The fundamental problem of developmental biology is to understand the interplay between the genetic instructions and the mechanisms by which those instructions are carried out.

In the language of genetics the word genotype is used to indicate the hereditary instructions passed on from one generation to another in the genes, while phenotype is the term given to the functioning organisms produced by those instructions. Biological development, therefore, consists of the production of phenotypes. The point made in the last paragraph is that the formation of the phenotype of one generation depends on the functioning of part of the phenotype of the previous generation (e.g., egg cell), as the mechanism that begins the interpretation of the instructions contained in the new organism’s genotype.

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