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

Vertebrate eggs can induce the reprogramming of transplanted somatic nuclei to enable the generation of all cell types of a cloned organism. However, the efficiency of nuclear reprogramming is low, and only a small proportion of the nuclear transfer embryos generated from differentiated cells reach a reproductive adulthood. How the egg achieves the erasure of the previous somatic cell identity and the establishment of totipotency only in some instances remains a question of fundamental importance. Epigenetic modifications were shown to be major roadblocks to reprogramming, but how these roadblocks resist removal by the egg factors and how they are instead propagated during early embryonic cell divisions to induce inappropriate expression of genes in nuclear transfer embryos is not known. This proposal aims at identifying the molecules in the egg that a) help to overcome the epigenetic barriers during successful reprogramming events and b) cause resistance when reprogramming fails. We will then c) interfere with these mechanisms to improve cell fate conversion. The gained molecular insights into cell fate reprogramming via the natural activities present in the egg can then be utilized to develop efficient reprogramming strategies for therapeutic purposes such as enhancing regeneration or improving cell replacement therapies.