One factor, not four like a majority of biologists throughout the world have said up until now, is sufficient to convert an adult stem cell into a cell that is similar to an embryonic stem cell. A recipe that is much more simple than what the scientific community has believed has been discovered by Hans Schöler and his colleagues, who include Italians ,Vittorio Sebastiano and Luca Gentile, from the Max Planck Institute for Molecular Biomedicine in Germany. The study, published in February’s edition of Cell, shows for the first time that nerve stem cells taken from an adult mouse can assume the characteristics of embryonic stem cells with the addition of only one transcription factor, or one gene that controls the activity of other genes.
The discovery comes after results already published in 2006 in the same journal, in which Shinya Yamanaka of Kyoto University in Japan announced having discovered that introducing four factors, Oct4, Sox2, Klf4, and c- , made it possible to reprogram adult cells, making them pluripotent cells (iPS, or induced pluripotent stem cells), which have characteristics similar to embryonic stem cells, which are able to differentiate in any cellular tissue in the body. In 2007, Yamanaka and his colleagues demonstrated that the same recipe, with four factors can also function with adult skin stem cells. Later studies demonstrated that the recipe could also function with two or three of the four genes, and now Schöler and his colleagues have demonstrated in this new study that in order to confer pluripotency to adult nerve stem cells, only Oct4 is necessary, the true driving force to convert adult nerve stem cells into iPS cells.
According to scientists, the discovery will aid in understanding what distinguishes embryonic stem cells, which are the origin of sperm and egg cells, from adult cells, but could also have important therapeutic implications in replacing damaged cells due to disease or trauma with reprogrammed cells. The cells, which researchers call “1F iPS” have demonstrated that they can differentiate into all three embryonic “primary germ layers”, which give rise to all of the organs and all of the tissues in the human body. These cells are not only able to differentiate efficiently into neural stem cells, cardiomyocytes, germ cells, and others, but, if they are injected under the skin in mice, they induce the development of specific tumors, called tetratomas, cancerous formations that contain tissue that represents all three of the embryonic germ layers. Experimentally, it has been observed that when 1F iPSs are injected into the embryo of a mouse, these cells infiltrate into the organs in formations that, once implanted, are transmitted through the germ layer to future generations.
The results of the study demonstrate that adult stem cells can be reprogrammed into pluripotent cells, iPSs, without c-Myc and Klf4, both potential oncogenes that can transform normal cells into cancerous cells. Limiting conversion factors is a positive development, explained Schöler, because it means inserting fewer genes into the genome resulting in fewer negative effects. “It is exciting to know that only one gene, Oct4, is sufficient to induce pluripotency,” concluded Schöler. “Future studies will demonstrate if it will be possible to use other sources of neural cells or progenitor cell populations, like mesenchymal stem cells derived from bone marrow or from human or mouse dental pulp to be reprogrammed into iPS cells, and if the expression of Oct4 can be obtained without using viral vectors, an important prerequisite to generate iPSs, which may be valid for therapeutic uses.