Stem cells: totipotent, pluripotent and multipotent
A stem cell is a cell (either adult or embryonic) that is capable of indefinite renewal through cell division and retention of its generic or unspecialized state while at the same time maintaining its potential to give rise to daughter cells of a more specialized type.
Classification of stem cells as totipotent, pluripotent and multipotent describes the breadth of the stem cells ability to create specialized cell types. Stem cells represent a continuum or spectrum from embryonic stem cells to adult stem cells. The primary distinguishing factor is plasticity – the stem cell’s capacity to differentiate into multiple specialized cell types.
Totipotent stem cells are known as the master cells of the body because they have the capacity to differentiate into the 216 specialized cell types that comprise the human body plus the placenta. A fertilized egg is an example of a totipotent cell.
Pluripotent stem cells are highly versatile cells and can give rise to any specialized cell type in the body except those needed to develop a fetus. Embryonic stem cells are pluripotent.
Multipotent stem cells can give rise to several specialized daughter cells but are limited to the particular tissue, organ or physiological system of origin. For example, hematopoietic stem cells can produce many types of blood cells in the circulatory system but cannot differentiate into a brain cell. Hematopoietic stem cells are an example of adult stem cells and are multipotent. Stem cells from umbilical cord blood are also multipotent based on evidence to date.
Take a look at totipotent, pluripotent and multipotent stem cells as they relate to the human development continuum:
What Are Stem Cells? An Overview
A stem cell is a cell that has the ability to divide (self replicate) for indefinite periods often throughout the life of the organism. Under the right conditions, or given the right signals, stem cells can give rise (differentiate) to the many different cell types that make up the organism. That is, stem cells have the potential to develop into mature cells that have characteristic shapes and specialized functions, such as heart cells, skin cells, or nerve cells.
Stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. In addition, in many tissues they serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.
Stem cells are distinguished from other cell types by two important characteristics. First, they are unspecialized cells capable of renewing themselves through cell division, sometimes after long periods of inactivity. Second, under certain physiologic or experimental conditions, they can be induced to become tissue- or organ-specific cells with special functions. In some organs, such as the gut and bone marrow, stem cells regularly divide to repair and replace worn out or damaged tissues. In other organs, however, such as the pancreas and the heart, stem cells only divide under special conditions.
The fertilized egg is said to be totipotent from the Latin totus, meaning entire because it has the potential to generate all the cells and tissues that make up an embryo and that support its development in utero. The fertilized egg divides and differentiates until it produces a mature organism. Adult mammals, including humans, consist of more than 200 kinds of cells. These include nerve cells (neurons), muscle cells (myocytes), skin (epithelial) cells, blood cells (erythrocytes, monocytes, lymphocytes, etc.), bone cells (osteocytes), and cartilage cells (chondrocytes). Other cells, which are essential for embryonic development but are not incorporated into the body of the embryo, include the extraembryonic tissues, placenta, and umbilical cord. All of these cells are generated from a single, totipotent cell the zygote, or fertilized egg.
Most scientists use the term pluripotent to describe stem cells that can give rise to cells derived from all three embryonic germ layers mesoderm, endoderm, and ectoderm. These three germ layers are the embryonic source of all cells of the body. All of the many different kinds of specialized cells that make up the body are derived from one of these germ layers (see Table). “Pluri” derived from the Latin plures means several or many. Thus, pluripotent cells have the potential to give rise to any type of cell, a property observed in the natural course of embryonic development and under certain laboratory conditions.
Embryonic Germ Layers From Which Differentiated Tissues Develop
| Embryonic Germ Layer | Differentiated Tissue |
|---|---|
| Endoderm | Thymus Thyroid, parathyroid glands Larynx, trachea, lung Urinary bladder, vagina, urethra Gastrointestinal (GI) organs (liver, pancreas) Lining of the GI tract Lining of the respiratory tract |
| Mesoderm | Bone marrow (blood) Adrenal cortex Lymphatic tissue Skeletal, smooth, and cardiac muscle Connective tissues (including bone, cartilage) Urogenital system Heart and blood vessels (vascular system) |
| Ectoderm | Skin Neural tissue (neuroectoderm) Adrenal medulla Pituitary gland Connective tissue of the head and face Eyes, ears |
Unipotent stem cell, a term that is usually applied to a cell in adult organisms, means that the cells in question are capable of differentiating along only one lineage. “Uni” is derived from the Latin word unus, which means one. Also, it may be that the adult stem cells in many differentiated, undamaged tissues are typically unipotent and give rise to just one cell type under normal conditions. This process would allow for a steady state of self-renewal for the tissue. However, if the tissue becomes damaged and the replacement of multiple cell types is required, mulipotent stem cells may become activated to repair the damage.
The embryonic stem cell is defined by its origin that is from one of the earliest stages of the development of the embryo, called the blastocyst. Specifically, embryonic stem cells are derived from the inner cell mass of the blastocyst at a stage before it would implant in the uterine wall. The embryonic stem cell can self-replicate and is pluripotent it can give rise to cells derived from all three germ layers.
The adult stem cell is an undifferentiated (unspecialized) cell that is found in a differentiated (specialized) tissue; it can renew itself and become specialized to yield all of the specialized cell types of the tissue from which it originated. Adult stem cells are capable of self-renewal for the lifetime of the organism. Sources of adult stem cells have been found in the bone marrow, blood stream, cornea and retina of the eye, the dental pulp of the tooth, liver, skin, gastrointestinal tract, and pancreas. Unlike embryonic stem cells, at this point in time, there are no isolated adult stem cells that are capable of forming all cells of the body. That is, there is no evidence, at this time, of an adult stem cell that is pluripotent.
Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic “somatic” or “adult” stem cells. Scientists discovered ways to derive embryonic stem cells from early mouse embryos nearly 30 years ago, in 1981. The detailed study of the biology of mouse stem cells led to the discovery, in 1998, of a method to derive stem cells from human embryos and grow the cells in the laboratory. These cells are called human embryonic stem cells. The embryos used in these studies were created for reproductive purposes through in vitro fertilization procedures. When they were no longer needed for that purpose, they were donated for research with the informed consent of the donor. In 2006, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells to be “reprogrammed” genetically to assume a stem cell-like state. This new type of stem cell, is called induced pluripotent stem cells (iPSCs).
Unique Properties of All Stem Cells
Stem cells differ from other kinds of cells in the body. All stem cells regardless of their source have three general properties: they are capable of dividing and renewing themselves for long periods; they are unspecialized; and they can give rise to specialized cell types.
Stem cells are capable of dividing and renewing themselves for long periods. Unlike muscle cells, blood cells, or nerve cells which do not normally replicate themselves stem cells may replicate many times, or proliferate. A starting population of stem cells that proliferates for many months in the laboratory can yield millions of cells. If the resulting cells continue to be unspecialized, like the parent stem cells, the cells are said to be capable of long-term self-renewal.
Scientists are trying to understand two fundamental properties of stem cells that relate to their long-term self-renewal:
- why can embryonic stem cells proliferate for a year or more in the laboratory without differentiating, but most non-embryonic stem cells cannot; and
- what are the factors in living organisms that normally regulate stem cell proliferation and self-renewal
Discovering the answers to these questions may make it possible to understand how cell proliferation is regulated during normal embryonic development or during the abnormal cell division that leads to cancer. Such information would also enable scientists to grow embryonic and non-embryonic stem cells more efficiently in the laboratory.
The specific factors and conditions that allow stem cells to remain unspecialized are of great interest to scientists. It has taken scientists many years of trial and error to learn to derive and maintain stem cells in the laboratory without them spontaneously differentiating into specific cell types. For example, it took two decades to learn how to grow human embryonic stem cells in the laboratory following the development of conditions for growing mouse stem cells. Therefore, understanding the signals in a mature organism that cause a stem cell population to proliferate and remain unspecialized until the cells are needed. Such information is critical for scientists to be able to grow large numbers of unspecialized stem cells in the laboratory for further experimentation.
Stem cells are unspecialized. One of the fundamental properties of a stem cell is that it does not have any tissue-specific structures that allow it to perform specialized functions. For example, a stem cell cannot work with its neighbors to pump blood through the body (like a heart muscle cell), and it cannot carry oxygen molecules through the bloodstream (like a red blood cell). However, unspecialized stem cells can give rise to specialized cells, including heart muscle cells, blood cells, or nerve cells.
Stem cells can give rise to specialized cells. When unspecialized stem cells give rise to specialized cells, the process is called differentiation. While differentiating, the cell usually goes through several stages, becoming more specialized at each step. Scientists are just beginning to understand the signals inside and outside cells that trigger each stem of the differentiation process. The internal signals are controlled by a cell’s genes. The external signals for cell differentiation include chemicals secreted by other cells, physical contact with neighboring cells, and certain molecules in the microenvironment. The interaction of signals during differentiation causes the cell’s DNA to acquire epigenetic marks that restrict DNA expression in the cell and can be passed on through cell division.
Many questions about stem cell differentiation remain. For example, are the internal and external signals for cell differentiation similar for all kinds of stem cells Can specific sets of signals be identified that promote differentiation into specific cell types Addressing these questions may lead scientists to find new ways to control stem cell differentiation in the laboratory, thereby growing cells or tissues that can be used for specific purposes such as cell-based therapies or drug screening.
Adult stem cells typically generate the cell types of the tissue in which they reside. For example, a blood-forming adult stem cell in the bone marrow normally gives rise to the many types of blood cells. It is generally accepted that a blood-forming cell in the bone marrow which is called a hematopoietic stem cell cannot give rise to the cells of a very different tissue, such as nerve cells in the brain. Experiments over the last several years have purported to show that stem cells from one tissue may give rise to cell types of a completely different tissue. This remains an area of great debate within the research community. This controversy demonstrates the challenges of studying adult stem cells and suggests that additional research using adult stem cells is necessary to understand their full potential as future therapies.
