This experiment investigated the role of the gene Ezh2 in stem cell biology. Students looked at microscopic images - comparing normal mouse stem cells with Ezh2 knockout cells. So what were their observations?
"Large colony of undifferentiated stem cells Some differentiated cells have appeared in gaps between the masses of cells. In the control...the gaps are empty."
"A lot of differentiation occurring when compared to control."
"The normal cells don't have many differentiating cells, but the cells without the Ezh2 gene ... have more differentiating cells, and they look bigger."
"Large colony of undifferentiated stem cells. Some differentiated cells have appeared in gaps between the masses of cells. In the control...the gaps are empty."
"A lot of differentiation occurring when compared to control."
"The normal cells don't have many differentiating cells, but the cells without the Ezh2 gene ... have more differentiating cells, and they look bigger."
The consensus was that the experiment showed that Ezh2 does probably have a role in controlling stem cell specialization, but what was their evidence?
“…the differences between the control cells and the cells affected by Ezh2 is great, it definitely plays a role in controlling stem cell properties.”
“There seem to be more cells differentiating in the test than in the control, so Ezh2 is affecting the cells.”
“It seems as if Ezh2 is involved in stem cell differentiation because in all the slides the Ezh2 knockout cells have more differentiating cells.”
“…the test cells (with Ezh2 removed) had more differentiating cells than the control cells.”
But as always in science there was some dissent!
“…both the control and test had differentiated cells present. Ezh2 just seemed to make the cells stay in their colonies rather than be single cells.”
We asked the students to give us their insights using these questions.
1) Do you think Ezh2 plays a role in controlling stem cell properties? What is your evidence?
“I do think that Ezh2 plays a role in controlling stem cell properties. When compared with controls, stem cells that had had the Ezh2 knocked out showed considerably more stem cell differentiation.”
“The experiment suggests that the removal of the Ezh2 gene allows differentiation to occur. This is because all of the mutant samples that had this gene removed exhibited some kind of cellular differentiation. “
“It may be playing a role, as all the mutant cells seem to be differentiating.”
“Yes as when the Ezh2 gene was removed there were far differentiating cells present that in the control slide. The evidence was the test sides showed single cells in the gaps of the colonies with nuclei present and they shape of the cell was flat and large which are signs of differentiation.”
2) Do you think it is likely to be the only factor controlling stem cell properties? What might the other factors be?
“No, it is likely that other chemical signals trigger differentiation. “
“No. Physical factors such as temperature may have an effect on stem cells, as well as chemicals such as hormones from within the body.”
“Temperature, pH, and if other cells are present in the culture.”
“No, other factors may contribute such as genes in the DNA.”
“…other ingredients in the cell food may have had an effect on the stem cell properties.”
“It is not likely that Ezh2 is the only factor controlling stem cell properties. Other factors could include the temperature the cells are being stored at, the concentration of stem cells or the type of stem cell.”
3) Does our experiment tell us what Ezh2 does?
“The experiment shows that Ezh2 has a correlation to limiting differentiation, however, it may not suggest a causation.”
“No. It does not show us the specific mechanism by which it inhibits stem cell activity.”
“Not specifically, but it does suggest that the gene has a role in cell differentiation.”
“Not clearly, but it does tell us that it may be involved in controlling cell differentiation.”
“No because there are many other factors that could be involved because the process is so complicated.”
4) How could you be more certain of your results?
“We could be more certain of our results by counting the exact number of differentiated cells to make a direct comparison that is not subjective.”
“Repeat the experiment and compare the results.”
“Repeat results, use a larger sample size to improve reliability.”
“By carrying out the experiment multiple times and bearing in mind some of the other factors that could be involved.”
“The results could be much more reliable by repeating the tests to be more certain of the findings.”
“Obtaining more results at higher magnification.”
“Do more repeats and control other variables.”
5) How might a stem cell be similar to a cancer cell?
“Stem cells and cancer cells have the ability to grow rapidly and continuously.”
“Uncontrollable growth.”
“There are no Hayflick limits in either.”
“Both stem cells and cancer cells can replicate outside of the body (given the right conditions). There may also be a similarity in the way that tumour cells produced from one form of tissue can metastasize and continue to grow within another tissue.”
Stem cells have a lot of potential for medicine. We frequently see news reports of the latest stem cell research, but not all the headlines are good. Scientists are trying to understand how to persuade specialised cells to become stem cells again and genes like Ezh2 may hold the key to doing this. If scientists can re-programme specialised cells, any cell could potentially be used to treat diseases. In the future patients might be able to give a simple blood sample, which could be used to create stem cells for their treatment. The patient would supply his or her own medicine!
These students gave us their ideas about the ethics of embryonic stem cell research and considered how the ability to re-programme specialized cells could address some of the scientific and ethical issues.
“This method might be preferable to using embryonic stem cells because it overcomes the ethical boundaries of using embryonic stem cells as treatment for illness. Many people believe that it is unethical to use embryonic stem cells for treatment because it involves the development of a zygote into a growing embryo, which many consider as a human being. Therefore producing embryos solely for medical treatment goes against ideas of sanctity of human life. However, if a person’s own blood/skin cells an be used and reprogrammed into stem cells again then we would not have the problem of whether to create embryos with a sole purpose for extracting ES cells to treat illnesses. Another reason this method might be preferable to using embryonic stem cells is because it would be easier and cheaper to extract body cells from the person needing treatment than from an embryo. Stem cells also may be able to be produced quicker, speeding up treatment.“
“Some people would find it more ethical, as they believe that an embryo has the same value as a human life.”
“In terms of ethics, this would be more preferable because it would mean no embryos are destroyed.”
“Embryonic stem cells are harder to get as you have create the embryo first by fusing sperm and egg. When embryonic stem cells are used the embryo must then be destroyed, this is killing possible human beings.”
“There are many ethical issues surrounding the use of stem cells, such as the religious questions which arise from their collection or the potential that each cell could grow into a human. Also, the ability to convert differentiated cells back into stem cells would be a lot less time consuming, cheaper, less difficult and ethically questionable to do.”
“Embryonic stem cells should be used as not only are they able to differentiate into any cell in the body but they are also cells of our own body and thus will not be rejected when used in treatment of the body.”
“Less ethical concerns No immunosuppressive drugs needed.”
“Reprogrammed tissue cells from a patient's own tissue will not be rejected by their immune system (same surface antigens).”
“Scientists can grow new cells for example, skin which can be grown from the same cells from the person who needs a skin transplant and therefore stops rejection. organs could be grown from a persons cells and therefore stored in case they need a organ transplant.”
“You would not have to kill a fertilised cell, which could potential turn into life. Also, in embryonic stem cells, we are limited in terms of availability, where as persuading specialized cells to become stem cells again means they are more available.”
