An adult human being contains well over 10 trillion cells and these cells are organized into tissues, which go on to form organs within organ systems. In order to create an organism as complex as a human being, each cell must perform a specialized function. In addition, the cells in an organ must be organized such that the organ can function properly. For example, the pancreas must create both digestive enzymes and endocrine hormones. The cells that synthesize digestive enzymes must be located such that the cell products can enter ducts to ultimately empty into the duodenum. As such, the cells that produce endocrine hormones must be in close proximity to a blood vessel to put their products into systemic circulation. In order for this to occur, the cell must be undergo determination and differentiation. Determination refers to the commitment of a cell to a particular function in the future.5 Before undergoing determination, the cell can become any cell type but after determination, the cell is committed to a specific lineage. If during cleavage, the existing mRNA and protein in the parent cell has been asymmetrically distributed between the daughter cells, the presence of specific mRNA and protein molecules may result in determination. Determination may also occur due to secretion of specific molecules from nearby cells. These molecules, also called morphogens, may cause nearby cells to follow a particular developmental pathway.5 Determination is a commitment to a particular cell type, but note that the cell has not yet actually produced the products it needs to carry out the functions of that cell type, that is the goal of differentiation. After a cell’s fate has been determined, the cell must begin to undertake changes that cause the cell to develop into the determined cell type. This includes changing the structure, function, and biochemistry of the cell to match the cell type through differentiation. When a cell is determined, it is committed to a particular cell lineage. When the cell differentiates, it assumes the structure, function, and biochemistry of that cell type. Cells that have not yet differentiated, or which give rise to other cells that will differentiate, are known as stem cells. Stem cells exist in embryonic tissues as well as adult tissues. The tissues a particular stem cell can differentiate into are determined by its potency. Cells with the greatest potency are called totipotent and include embryonic stem cells; totipotent cells can ultimately differentiate into any cell type, either in the fetus or in the placental structures. After the 16-cell stage, the cells of the morula begin to differentiate into two groups: the inner cell mass and the trophoblast cells. After a few more cycles of cell division, these totipotent cells start to differentiate into the three germ cell layers. At this stage, the cells are said to be pluripotent; these cells can differentiate into any cell type except for those found in the placental structures.5 Finally, as the cells continue to become more specialized, they are said to be multipotent. Multipotent stem cells can differentiate into multiple types of cells within a particular group. For example, hematopoietic stem cells are cells that are capable of differentiating into all of the cells found in blood, including the various types of white blood cells, red blood cells, and platelets—but not into skin cells, neurons, or muscle cells. While we use all of these different terms to describe potency, it is important to recognize that potency is a spectrum, not a series of strict definitions. Stem cells exist not only in embryos, but also in adults as we have stem cells that give rise to skin, blood, and the epithelial lining of the digestive tract, among others. Stem cells are able to differentiate into different cell types. The potency of the stem cell determines how many different cell types a stem cell can become. As cells become more differentiated, the potency of the cell gets narrower (from totipotent to pluripotent to multipotent).
The determination and differentiation of a cell depends on the location of the cell itself as well as the identity of the surrounding cells. The developing cell receives signals from organizing cells around it and may also secrete its own signals. Surrounding tissues induce a developing cell to become a particular cell type via inducers. The term inducer may also refer to the cell secreting the signal. The cell that is induced is called a responder (responsive cell). To be induced, a responder must be competent, or able to respond to the inducing signal. Cell–cell communication can occur via autocrine, paracrine, juxtacrine, or endocrine signals. Autocrine signals act on the same cell that secreted the signal in the first place. Paracrine signals act on cells in the local area. Juxtacrine signals do not usually involve diffusion, but rather feature a cell directly stimulating receptors of the adjacent cell. Finally, endocrine signals involve secreted hormones that travel through the bloodstream to a distant target tissue. Inducers are commonly growth factors, which are peptides that promote differentiation and mitosis in certain tissues. Most growth factors only function on specific cell types or in certain areas, as determined by the competence of these cells. In this way, certain growth factors can code for particular tissues.
Cells must be able to disconnect from adjacent structures and migrate to their anatomically correct location. For example, the anterior pituitary gland originates from a segment of oral ectoderm and must migrate from the top of the mouth to its final location just below the hypothalamus. Neural crest cells also undergo extensive migration. These cells form at the edge of the neural folds during neurulation and then migrate throughout the body to form many different structures, including the sensory ganglia, autonomic ganglia, adrenal medulla, and Schwann cells, as well as specific cell types in other tissues, such as calcitonin-producing cells of the thyroid, melanocytes in the skin, and others.
During the process of apoptosis, the cell undergoes changes in morphology and divides into many self-contained pieces called apoptotic blebs, which can then be digested by other cells. This allows for recycling of materials. Because the blebs are contained by a membrane, this also prevents the release of potentially harmful substances into the extracellular environment. This is different from necrosis, which is a process of cell death in which a cell dies as a result of injury. In necrosis, internal substances can be leaked, causing irritation of nearby tissues, or even an immune response.
Regenerative capacity, or the ability of an organism to regrow certain parts of the body, varies from species to species. Some species, such as salamanders and newts, have an enhanced capacity to regenerate because they retain extensive clusters of stem cells within their bodies. When regeneration is required, these stem cells can then migrate to the necessary part of the body to initiate regrowth. These species are said to undergo complete regeneration, in that the lost or damaged tissues are replaced with identical tissues.6 In contrast, incomplete regeneration implies that the newly formed tissue is not identical in structure or function to the tissue that has been injured or lost. Humans typically exhibit incomplete regeneration in response to injury. However, in humans, regenerative capacity varies by the tissue type. Liver tissue has a high regenerative capacity, often able to undergo extensive regeneration following injury or loss. For example, living donors are often able to donate up to 50 percent of their liver tissue because their own livers will regenerate the missing portion. Unfortunately, the heart has little, if any, regenerative capacity, and scarring often results following an injury such as a heart attack. The kidneys have moderate regenerative capacity and are able to repair nephrons after injury to the tubules; however, this regenerative capacity is easily overwhelmed, and kidney failure may result.
As organisms age, changes occur in both molecular and cellular structure. This results in disruption of metabolism and, eventually, death of the organism. Senescence, or biological aging, occurs as these changes accumulate and can occur at the cellular and organismal level.6 At the cellular level, senescence results in the failure of cells to divide, normally after approximately 50 divisions in vitro. Research has demonstrated that this may be due to shortened telomeres, or the ends of chromosomes. Telomeres prevent the loss of genetic information from the ends of chromosomes and help prevent the DNA from unravelling. Their high concentration of guanine and cytosine enables telomeres to knot off the end of the chromosome. Telomeres are difficult to replicate, however, so they shorten during each round of DNA synthesis. Eventually, the telomeres become too short, and the cell is no longer able to replicate. Some cells, including germ cells, fetal cells, and tumor cells, express an enzyme known as telomerase. This enzyme is a reverse transcriptase that is able to synthesize the ends of chromosomes, preventing senescence. Telomerase allows for cells to divide indefinitely and may play a role in the survival of cancer cells. At the organismal level, senescence represents changes in the body’s ability to respond to a changing environment. Aging is complex and often involves not only cellular senescence but also the accumulation of chemical and environmental insults over time.
1) Maton A, Hopkins JJ, LaHart S, Quon Warner D, Wright M, Jill D (1997). Cells: Building Blocks of Life. New Jersey: Prentice Hall. pp. 70–4
2) Wilbur, Beth, editor. The World of the Cell, Becker, W.M., et al., 7th ed. San Francisco, CA; 2009.
3) Kent, M. (2000). Advanced Biology. Pages 246 -247. Oxford University Press.
4) M.B.V. Roberts, J. M. (1985) Biology for CXC. Pages 266 – 267. Cheltenham: Thomas Nelson and Sons Limited.
5) Slack, J.M.W. (2013) Essential Developmental Biology. Wiley-Blackwell, Oxford.
6) Hayflick L; Moorhead PS (December 1961). “The serial cultivation of human diploid cell strains”. Exp. Cell Res. 25: 585–621.