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.