www.BioTopics.co.uk
Site author Richard Steane
The BioTopics website gives access to interactive resource material, developed to support the learning and teaching of Biology at a variety of levels.

Most of a cell's DNA is not translated
(potency varies from cell to cell)

Every cell of the body has DNA in its nucleus coding for all the proteins the body needs.

However, most of a cell's DNA is not translated. Depending on the development of cells within an organism, different sections of DNA (genes) may need to be brought into action to produce specific proteins.

For instance, various glands along the alimentary canal secrete digestive enzymes which are proteins, specific to that area only. Within skin follicles, hairs are continuously produced, and these are composed of the protein keratin.

Red blood cells are the only cells that need the protein haemoglobin, but they are almost the exception to the rule in that they do not contain a nucleus. However they develop from a cell that does have a nucleus, and the cellular machinery to transcribe the haemoglobin genes into mRNA which is then translated into haemoglobin.

Turning on and turning off genes - for positive and negative outcomes

Although we can now identify genes together with their location on the different chromosomes, and a certain amount is known about the mechanism of turning them on and off, there is less certainty about the initiation of these processes in different tissues of the body as differentiation takes place.

The body obviously needs some flexibility in this area to allow worn-out cells to be replaced.

But cancer cells are characterised by genes being active in inappropriate circumstances, and degenerative diseases are often caused by genes being inactive, or overactive, producing excess amounts of certain proteins.
This topic has connections with Nucleic acid structure, DNA replication (in Biological Chemicals) and DNA and protein synthesis (in Genetic information). It continues with 'Regulation of transcription and translation' ( in The control of gene expression) (links below).

Cells' potential varies

The word potency implies strength or power, and it may be modified by various prefixes, which indicate the differentiation possibilities:
Totipotent means able to develop into all body cells, as well as the placenta
Pluripotent means able to develop into any of the cell types of the body
Multipotent means able to develop into a limited number of cell types in a particular lineage
and Unipotent means able to develop into a single cell type.

Totipotent cells

can divide and produce any type of cell.

At the start of life, the fertilised egg or zygote obviously has the potential to divide and produce any cells within the body (of an animal). This includes the three tissue layers established in the embryo - ectoderm, mesoderm and endoderm - as well as extra-embryonic tissues such as the placenta. These somatic (body) cells are derived by mitotic division of this single cell, and germ line cells (sperms and eggs) are derived by meiotic division.

In fact totipotent cells occur only for a limited time in mammalian embryos, within the 'ball of cells' stage known as a morula. As they develop, cells transcribe and translate just a certain amount of their DNA, producing proteins that are necessary for their specialisation as they differentiate into different cell types, and there are more than 200 types of cells in the human body.

Plants also develop from totipotent cells which then differentiate into different tissues composed of specialised cell types. In mature plants, many cells remain totipotent. When given the correct conditions in the laboratory, such as the correct concentration of growth factors, these cells have the ability to develop into whole plants or into plant organs.

Triploblasty

This is the existence of three tissue layers in the early embryo of many groups of organisms within the animal kingdom.

Pluripotent, multipotent and unipotent stem cells

are found in mature mammals. Stem cells have the potential for unlimited cell division, but after mitotic division one of the two resulting cells usually remains as a stem cell, able to divide again, whilst the other develops into other cells, generally with less potential for variation.

Embryonic stem cells divide producing other cell types during normal growth and development. After the completion of growth, a few mature somatic stem cells in the body retain the ability to divide into other cell types, and they are used to repair damage and replace cells.

Cells produced after approximately the first 4 days from fertilisation have a more limited potential: these are called pluripotent cells.

Pluripotent stem cells can differentiate into any of the body layers ectoderm, mesoderm or endoderm, but not placenta.

Multipotent stem cells are sometimes described as lineage specific, e.g. Haematopoietic Stem Cells (HSCs) within the bone marrow have a limited differentiation potential and can develop only into cells within their tissue/cell types, in this case blood cells: red blood cells, and various white cells. Other alternatives (each with different potential outcomes) are neural stem cells and mesenchymal stem cells.

Unipotent stem cells are more limited, and can only produce a single cell type, such as skin cells, which are continuously wearing away at the surface and need to be replaced from below. Cardiomyocytes - cells making the muscular walls of atria and ventricles of the heart - are another example.

Stem cells for meat products

There is a potential market for meat substitute products based on animal stem cells, cultured in media similar to that used in laboratories.

In a sense, it does not differ greatly from fermentation processes used to produce alcoholic drinks. If this is accepted, there will be less need to raise and regularly slaughter actual animals. It is potentially a less environmentally damaging alternative.

However, there are a lot of issues involved . . .

Induced pluripotent stem cells (iPS cells)

As their name implies, these can be produced in the laboratory from other adult body cells (somatic cells) using protein transcription factors.

The first iPS cells - murine ES (embryonic stem) like cell lines - were derived from mouse embryonic fibroblasts (MEFs) and skin fibroblasts by using retroviruses to insert four transcription factor genes into the cells.

The transcription factors attach to the promoter region of a gene, and either stimulate or inhibit the transcription of the appropriate section of DNA which produces proteins such as enzymes which are specific to the transformed cell type.




The primary transcription factor used to create induced pluripotent stem cells is Oct4 (octamer-binding transcription factor 4). This has an octamer motif, a particular DNA sequence of AGTCAAAT that binds to target genes and activates or deactivates gene expression in various ways.

Sox2 (Sex-determining region Y-box 2) is one of the key transcription factors that play an essential role in maintaining pluripotency of stem cells. Sox2 interacts with Oct4 to form a binary complex, which then recruits other nuclear factors to activate pluripotent gene expression and repress genes involved in differentiation.

KLF4 (Kruppel-like factor 4) is a member of the KLF family of zinc finger transcription factors. KLF4 is involved in the regulation of proliferation, differentiation, apoptosis and somatic cell reprogramming. Evidence also suggests that KLF4 is a tumour suppressor in certain cancers, including colorectal cancer.

c-Myc plays a major role in the generation of induced pluripotent stem cells (iPSCs). It is one of the original factors discovered by Yamanaka et al. to encourage cells to return to a 'stem-like' state alongside transcription factors Oct4, Sox2 and Klf4. It has since been shown that it is possible to generate iPSCs without c-Myc

Use of stem cells in treating human disorders

There have been a number of situations where it is thought that stem cells may be used to treat human disorders.

These include replacement of cells damaged by injury, degenerative disease or genetic defects.

Examples include
neurones in dementia diseases (Parkinson's, Alzheimer's)
retina cells in macular degeneration, colour blindness
pancreas cells influenced by autoimmune disease (type I diabetes)
Blood - variations in haemoglobin protein structure:
sickle cell disease
thalassemia
Severe Combined Immunodeficiency (SCID), an inherited primary immunodeficiency disease - caused by mutations in genes involved in the development and function of immune cells - principally T-lymphocytes
heart muscle cells

Sources of stem cells

Bone marrow transplants

Embryonic stem cells

Umbilical cord cells

Adult stem cells

Transformed stem cells

Ethical issues

Some of these are subject to ethical considerations.

In particular cells of embryonic origin are questioned by some if they come from human tissue obtained following termination of pregnancy: (elective?) abortions.

Similarly, 'leftover' human embryos following in vitro fertilisation are less unacceptable to some, although they clearly represent a potential human life.

Of course there are a number of issues regarding the use of human tissue. The well-known HeLa cell line has been used for many purposes in laboratories, but it was not obtained as a result of 'informed consent'.

Similarly, embryos do not give consent.

Bone marrow transplants are generally arranged following protracted screening processes designed to find donors that are clossely matched to recipients - blood and tissue typing.

Umbilical cord stem cells are fairly easily persuaded to differentiate into other cells, but they only reliably match with their donors, and they do not provide large numbers of cells. However, they are sometimes preserved in liquid nitrogen if it is thought that children will need some medical treatment which could be assisted by use of this material.

Umbilical cords and placentas are normally disposed of as waste following the birth of children.

Some of these cells after introduction to the body may develop into cancerous tumours.

Other related topics on this site

(also accessible from the drop-down menu above)

This series (The control of gene expression)
Base sequence alteration
Cell potency
Regulation of transcription and translation
Gene expression and cancer

Genetic information
DNA, genes and chromosomes
DNA and protein synthesis
Genetic diversity
Genetic diversity and adaptation
Investigating diversity

Control of heart rate - see the Cardiac myocytes - muscle cells - contracting independently.

Web references



Cardiomyocyte differentiation of mesenchymal stem cells from bone marrow: new regulators and its implications

Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise

IPS Cells or Induced Pluripotent Stem Cell FAQs

Embryonic Stem Cells and the Germ Cell Lineage

Describing the Stem Cell Potency: The Various Methods of Functional Assessment and In silico Diagnostics

Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise

IPS Cells or Induced Pluripotent Stem Cell FAQs

Alzheimer's Society's view on stem cell research

Is there a cure for dementia?

Embryonic Stem Cells: New Possible Therapy for Degenerative Diseases That Affect Elderly People

Cauliflower Cloning - Tissue Culture and Micropropagation

Cultured meat from muscle stem cells: A review of challenges and prospects

Out of the lab and into your frying pan: the advance of cultured meat

No-kill lab-grown meat to go on sale for first time

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