ReproMech · The Molecular Mechanisms of Cell Fate Reprogramming in Vertebrate Eggs

The Molecular Mechanisms of Cell Fate Reprogramming in Vertebrate Eggs

During embryonic development, cells become increasingly committed to a certain cell fate. They rarely, if ever, change to another type. For example, as skin cell do not naturally change to, or give rise to a brain cell. However, this stable commitment of a cell can be reverted by certain experimental procedures, as for example when the nucleus of a specialised cell is transplanted to an enucleated egg. During this reprogramming, the gene expression pattern of the differentiated cell can be changed to that of an embryonic cell. This process is of interest because identifying how reprogramming takes place can help us to understand how cells maintain their identity. This is important because many pathological conditions arise from loss of cell identity. Second, the embryonic stem cells that can be obtained by reprogramming a specialised cell of one kind, e.g. a skin cell, can then be made to produce healthy specialized cells of an other kind, e.g. brain cells. This has potential application in cell-replacement therapy, where these cells can compensate the loss of irreversibly damaged or defective cells. It might be possible to derive replacement heart, neuronal or pancreatic cells from another cell type of the same individual, thereby avoiding the need for immunosuppression treatments. Despite its enormous potential, the usefulness of this approach is limited by its low efficiency, as only a small number of cells can be fully reprogrammed. The reason why adult body cells like skin do not respond to nuclear reprogramming is likely related to an inherent resistance of a specialized kind of cell to change to a totipotent kind. The goal of our project was to elucidate the factors responsible for inherent resistance of specialized cells, as well as the molecules present in vertebrate eggs that can in some cases overcome these barriers to reprogramming. Once this is understood on a molecular level, we aimed at lowering the resistance factors and increasing the reprogramming molecules, so that reprogramming can become more efficient. We used nuclear transplantation of specialised cell nucleus to Xenopus eggs as a model system to understand this process.Outcomes of this study will in the future help to identify treatments that can improve the generation of high quality embryonic cells useful for cell replacement. Furthermore, our results will help to gain a better insight into the mechanisms important for cellular memory and the stability of cell differentiation during normal development and disease.

Data: CORDIS, © European Union