Jumping Genes and Stem Cells

I have always held a fascination for transposons, or jumping genes as they are sometimes called. Part of this interest may be due to my background in Drosophila genetics, where a transposon called a P element has been used extensively for genetic manipulation of flies for years. But also there is the fact that P elements appears to have made the jump into Drosophila melanogaster only recently (with in the past 50 years). From an evolutionary perspective this is fascinating as it allows us to study how a genome (in this case Drosophila) responds to the introduction of a new transposon.

However, On another front, the study of transposons joined forces with the study of stem cells this week. Even though President Obama has reversed the ban on using embryonic stem (ES) cells in research, scientists are still actively pursuing methods of generation stem cell lines. of particular interest are the induced pluripotent stem cells (iPS cells - see "This Isn't Science Fiction Anymore"). iPS cells are adult stem cells that have been convinced to revert back to a more generalized (less specialized) state. Although iPS cells have only been around for a few years, they have created a definite interest in the scientific community. If a method of making iPS cells was simplified - then it may be possible to make stem cells out of almost any human cell type. This would practically eliminate the need for embryonic (ES) stem cells and open up new avenues for genetic research.

One of the main problems with the generation of iPS lines has been the genetic vector used to alter the cells. For the past few years this has focused almost exclusively on the use of viruses. The main problem with viruses has been the fact that they are very disruptive to genomes. When a virus integrates itself into the genome it has the potential to disrupt important genes or their regulatory regions. But there is now another way and it involves the use of transposons. Once of the benefits of the transposon is that it carries a gene called transposase, which is what promotes the movement of the transposon in the genome. It also means that the location of the transposon is transient - it can move in and then move back out again. Like viruses, transposons can be genetically engineered to contain other genes, in this case the genes to make a cell pluripotent. One of the transposons that has been selected to do this is appropriately named piggyBac. piggyBac is a rather large transposon (around 2,400 base pairs in length) that has been used in the past to perform genetic transformation in fruit flies and other insects.

What is now possible, at least in mouse trials, is to deliver a genetically engineered transposon containing genes for pluripotency into a cell. Then, once the genes have been expressed, and the cell has undergone a transformation into a stem cell, the transposon can be activated and the genes removed. Thus, if the transposon inadvertently inactivated a gene of importance, it may be removed from the gene with very little consequence. By doing this geneticists hope to greatly increase the potential of using iPS cells in research.

This Isn't Science Fiction Anymore

Sometime an event occurs which makes it actually look like I might know what I am talking about.....

This past week in my human genetics class, we discussed the possibility of turning back the clock on adult stem cells to make them behave like embryonic stem cells. The lure of embryonic (or ES cells) is that they have not yet realized their genetic destiny, and therefore have the potential to become any stem cell. Of course, the main problem has been where ES cells were obtained from - most cells come from left-over in vitro fertilization (IVF) events, and some people have expressed a concern over the ethical use of these cells.

In the December 10th edition of Science (vol 322, issue 5099), the editors of the journal awarded the 2008 Breakthrough of the Year to the process that generates an induced pluripotent stem cell, or iPS. iPS cells are adult stem cells that have been genetically altered to behave like ES cells - opening up the possibility that they may be developed as a alternative source of stem cells. Furthermore, research in this area has suggested that it may be possible to develop iPS cells as a form of treatment for a wide variety of diseases, including Down Syndrome, Huntington disease, and juvenile diabetes. Anyone who has an interest in stem cells, and the future of medicine, should definitely read this article. Sometimes the facts are more interesting than the fiction!