Mammalian genes induce partially reprogrammed pluripotent stem cells in non-mammalian vertebrate and invertebrate species

Stem cells are ‘pluripotent’—in other words, they have the potential to become many other cell types. This ability makes them extremely valuable for research. They also hold substantial promise for medical applications, since they can be used to replace cells lost or damaged by disease or injury. Embryos represent a rich source of stem cells; however, obtaining these cells from human embryos raises obvious ethical and practical concerns, and they have also been difficult to isolate from many species. A recent discovery circumvented these issues for humans and several mammalian species commonly studied in the laboratory. This technique can turn cells from adult mammals into ‘induced pluripotent stem cells’, or iPSCs, by switching on four genes. Nevertheless, no analogous method has yet been established to create similar cell populations in non-mammalian organisms, which are also important models for human development and disease. Now, Rossello et al. have shown that cells from both invertebrate and non-mammalian vertebrate species—including birds, fish and insects—can be reprogrammed into cells that closely resemble iPSCs. Intriguingly, these cells were created by switching on the same four genes that generate iPSCs in mammals, even though vertebrates and invertebrates are separated by around 550 million years of evolution. Rossello et al. used a viral vector that carries the four stem-cell genes (from the mouse) into target cells from the different species. The genetically altered cells developed into iPSC-like cells with many of the characteristics of natural mammalian and bird stem cells. To confirm that the cells were pluripotent, Rossello et al. first showed that the cells could develop into primitive early embryos called embryoid bodies. For the vertebrate species tested, the embryoid bodies contained cells from each of the three main vertebrate embryo cell types. Secondly, iPSC-like cells from two organisms—chicks and zebrafish—formed various mature cell types when injected into developing chick or zebrafish embryos. These results have two important implications. They suggest that the genetic mechanisms by which cells can be reprogrammed into a stem-like state have been conserved through 550 million years of evolution; additionally, they demonstrate that stem-like cells can be generated from important experimental organisms, and provide an important tool for both biological and biomedical research.