Three years ago, Kyoto University scientist Shinya Yamanaka made induced pluripotent stem cells (iPSCs) by inserting four genes into skin cells from laboratory mice. To get these genes into cells he used genetically engineered retroviruses, which insert copies of genes directly into the chromosomes of the cells they infect. In order to convert the skin cells into iPSCs, he had to infect the cells with four different recombinant viruses, and subject the cells to four different insertion events. Because retroviruses randomly insert into the gene, there is the possibility that they could insert their DNA right in the middle of an active gene. Thus Yamanaka’s procedure left people worried about making mutations in tumor suppressor genes or other genes necessary for life. If iPSCs were going to be used for clinical purposed, then how could such a procedure be used in the clinic if it was so potentially dangerous?
Now two labs have shown that you can do the same experiment by inserting one piece of DNA to do the same job. Rudolf Jaenisch’s lab at MIT and Konrad Hochedlinger at Harvard University have combined the four mouse reprogramming genes onto a single piece of DNA, known as a cassette, and inserted it at a single locus in the mouse genome. The mice with the insert were bred, and their somatic cells were transformed into iPS cells following the addition of the antibiotic doxycycline, which triggers the cassette to express the four reprogramming genes. This innovation saves time and money and brings iPSCs one step closer to clinical trials.
One group of experiments that scientists hope to do with these newly made mouse strains is test the ability of iPSCs to form particular cell types versus traditionally made embryonic stem cells (ESCs). In a study published earlier this year in Cell Stem Cell, hundreds of genes are differentially expressed between iPSCs and ESCs (Chin, M. H. et al. (2009) Cell Stem Cell 5, 111-123). Another study in Nature showed that iPS cells are not as efficient as embryonic stem cells at differentiating into all cell types (Zhao, X.-Y. et al. (2009) Nature 461, 86-90).