Description du projet
Des cellules corporelles transplantées font table rase pour repartir à zéro
Les ovules et les spermatozoïdes diffèrent de toutes les autres cellules (somatiques) du corps d’un vertébré. Il semble donc assez miraculeux qu’un ovule fécondé produise toutes les cellules somatiques différenciées et variées qui vont former les tissus, les organes et les systèmes organiques. Cette capacité est appelée totipotence. Les ovules peuvent également reprogrammer des noyaux somatiques transplantés pour rétablir la totipotence et permettre la production de tous les types de cellules dans un organisme cloné, ce qui offre un potentiel extraordinaire pour la régénération des tissus et les applications cliniques. Améliorer l’efficacité de ce processus par la compréhension des mécanismes de reprogrammation du destin cellulaire sera au cœur de l’ambitieux projet ReproMech, financé par l’UE.
Objectif
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.
Champ scientifique
Programme(s)
Régime de financement
MSCA-IF-EF-ST - Standard EFCoordinateur
85764 Neuherberg
Allemagne