Define stem cells and its characteristics.
A stem cell is an unspecialized cell from the embryo, fetus, or adult that:
● under certain conditions, has self–renewal capability by reproducing itself for long periods or, in the case of adult stem cells, throughout the life of the organism, and
● can differentiate whereby unspecialized cells give rise to specialized cells that make up the tissues and organs of the body.
● possess large nuclear to cytoplasmic ratio.
Thus, stem cells can (a) replenish their own population and to (b) generate cells that travel down various differentiation / developmental pathways.
Explain in detail how stem cells are unspecialised.
● does not have any tissue-specific structures that allow it to perform specialized functions.
● However, unspecialized stem cells can give rise to specialized cells (specialization / differentiation.)
Explain how stem cells are capable of long term self renewal.
● Unlike muscle cells, blood cells, or nerve cells—which do not normally replicate themselves—stem cells may replicate many times. Ie proliferation
● 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 by mitotic divisions.
Explain how stem cells can give rise to specialised cells.
Signals from inside and outside cells trigger stem cell differentiation.
Internal signals: differential gene expression occurs when certain genes become activated and other genes become inactivated in an intricately regulated fashion — differentiated cell develops specific structures and performs certain functions.
External signals: chemicals secreted by other cells, physical contact with neighbouring cells, and certain molecules in the *microenvironment (nutrients and growth factors that are present in the surrounding fluid of the cell within an organism or in vitro in lab conditions.)
What is stem cell potency?
Range of cell types to which a stem cell can give rise to.
It is determined by the number of possible pathways that it can take in its subsequent development, through the process of specialization/differentiation
It reflects the differential potential of the stem cell.
Describe totipotent stem cells.
(Formed immediately upon fertilization, up to first 5 days after fertilization — consist ONLY of ZYGOTIC stem cells)
● Have the ability to give rise to all cell types that make up an organism.
● They exist as the fertilized egg (zygote) and the first few cells produced when the zygote divides rapidly by mitosis to form a compact ball of cells called morula.
● In mammals, such cells have the potential to differentiate into any cell type in the adult body AND any cell of the extra-embryonic membranes (e.g. placenta).
● Hence totipotent stem cells occur at the earliest stage of embryonic development; before the blastocyst stage. These totipotent cells have the potential to develop into a fetus when they are placed into the uterus via in- vitro fertilization (IVF) technique.
Describe pluripotent stem cells.
(Formed from 5 to 7 days after fertilisation — mainly embryonic stem cells)
● Descend from totipotent stem cells — give rise to types of cells that develop from the three germ layers (mesoderm, endoderm, and ectoderm) from which all the cells of the body arise.
● They do not have the potential to make differentiated cells that form the extra-embryonic membranes
● Embryonic Stem Cells
● The only known sources of human pluripotent stem cells are those isolated and cultured from inner cell mass of early human embryos and from fetal tissue that was destined to be part of the gonads.
Describe multipotent stem cells.
Formed after 7 days upon fertilisation
Descend from pluripotent stem cells and can differentiate into many cell lines within a specific type of tissue eg Adult stem cells
Can only differentiate into a limited number of cell types.
Multipotent stem cells are found in adult animals; perhaps most organs in the body (e.g., brain, liver) contain them where they can replace dead or damaged cells. These adult stem cells may also be the cells that upon accumulation of sufficient mutations, can produce a clone of cancer cells.
Describe how stem cells progressively become more differentiated.
As pluripotent cells themselves give rise to more pluripotent stem cells, they can also generate committed stem cells. Committed stem cells can give rise to a smaller population of cells. This usually involves formation of an intermediate progenitor cell. To some extent, progenitor cells are similar to stem cells, particularly adult stem cells. They can divide a number of times and may even have a very limited capacity for self-renewal. However, with each successive division, the cells usually become progressively more differentiated.
Describe committed stem cells, with the help of an example.
Committed stem cells are those that have a more limited pathway of development compared to pluripotent cells and are destined to produce a specific group of cells.
For example, one type of committed stem cell, the hemangioblast stem cell, gives rise to all the blood vessels, blood cells and lymphocytes.
Committed stem cells can give rise to more specifically committed stem cells or it can generate what are called progenitor cells (aka precursor cells).
Describe precursor/progenitor cells,
Typically, stem cells generate intermediate cell type(s) before they achieve their fully differentiated
state — precursor or progenitor cell. Progenitor or precursor cells in fetal or adult tissues are partly differentiated cells that divide and give rise to differentiated cells. Such cells are usually regarded as “committed” to differentiating along a particular cellular development pathway.
● A precursor / progenitor cell:
- usually shows some evidence of differentiation, although the process is not complete until the fully differentiated cell has been formed.
- is committed to a limited number of pathways of differentiation / development.
- is more limited in developmental pathways than a multipotent stem cell.
What is the significance of mitotic divisions of stem cells?
mitotic division of stem cells (1) preserves a population of undifferentiated cells while (2) steadily producing a stream of differentiating cells. Although some types of precursor cells can divide symmetrically to form more of themselves, they do so only for limited periods of time.
Describe the defining properties of embryonic stem cells.
Derived from embryos.
1. Capable of undergoing an unlimited number of symmetrical divisions without differentiating
(long-term self-renewal).
2. Exhibit and maintain a stable, full (diploid), normal complement of chromosomes (karyotype).
3. Can give rise to differentiated cell types that are derived from all three primary germ layers of the embryo (endoderm, mesoderm, and ectoderm).
4. Capable of developing into all fetal tissues during development.
5. Clonogenic i.e. a single ESC can give rise to a colony of genetically identical cells, or clones, which have the same properties as the original cell.
6. Unlike adult stem cells, they are easy to obtain pure and can be cultivated in large numbers.
Describe adult stem cells and its defining properties.
● An adult stem cell is an undifferentiated cell found among differentiated cells in a tissue or organ, can renew itself, and can differentiate to yield the major specialized cell types of the tissue or organ.
Adult stem cells can undergo cell division to renew their cell numbers (long term self renewal, clogenic) and under certain circumstances, they will mature into fully differentiated cells with mature phenotypes that are fully integrated into the tissue and are capable of specialised functions that are appropriate for the tissue.
● Adult stem cells are rare. Furthermore, adult stem cells are dispersed in tissues throughout the mature animal and behave very differently, depending on their local environment. There are many different types of stem cell, each restricted in the types of specialized cell it can give rise to; At any time, stem cell numbers in the body are very low making these cells extremely difficult to identify and purify. In addition, many stem cell types do not grow well in culture where they also often lose their distinctive cellular properties.
● The primary roles of adult stem cells in a living organism are to:
⮚ maintain and repair the tissue in which they are found, and
⮚ replace cells that die because of injury or disease.
● origin of adult stem cells in mature tissues is unknown. At this point in time, there are no isolated adult stem cells that are capable of forming all cells of the body
There are a very small number of adult stem cells in each tissue and are thought to reside in a specific area where they remain quiescent for many years until they are activated by disease or tissue injury.
Describe hematopoietic stem cells.
They are relatively accessible and can be grown in culture.
HSCs are constantly being generated in the bone marrow where they differentiate into mature types of blood cells. The primary role of HSCs is to replace blood cells. These stem cells are self-renewing and are the precursors of progenitor cells that are committed to one of the hematopoietic lineages at a later stage — lymphoid, myeloid and erythroid lineage.
Describe the different lineages hematopoietic stem cells can undergo.
Lymphoid: Produces a type of white blood cells, called lymphocytes, which include the two antigen-specific cell types of the immune system, the B and T lymphocytes.
Myeloid: Gives rise to the rest of the white blood cells which all derive from the bone marrow in adults.
● They include eosinophils, neutrophils, basophils (collectively known as granulocytes or polymorphonuclear leukocytes), mast cells, and monocytes.
● Leukocytes are mobile units of the body’s immune system. They function as:
⮚ defence against pathogen invasion by phagocytosis,
⮚ identification and destruction of cancer cells that arise within
the body,
⮚ the “clean-up crew” to remove / phagocytize debris from
dead / injured cells during wound healing / tissue repair.
Erythroid: Yields the red blood cells, or erythrocytes; and the megakaryocytes, which give rise to blood platelets.
Compare B lymphocytes and T lymphocytes.
B lymphocytes: White blood cells that come from the bone marrow. As part of the immune system, B lymphocytes make antibodies and help fight infections. Also called B cells. Develop in the bone marrow
T lymphocytes: White blood cells that attack virus-infected cells, foreign cells, and cancer cells. T lymphocytes also produce a number of substances that regulate the immune response. Also called T cells. Develop in the thymus from precursors that originate from the multipotent stem cells in the bone marrow and migrate from the bloodstream into the thymus
Both B and T lymphocytes undergo a further terminal differentiation after they encounter antigens