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Communication dans un congrès

Reprogramming somatic nuclei into embryonic nulei through nuclear transfer and the stem cell potential of the derived cell lines

Abstract : Reprogramming refers to the multistep process that allows a cell nucleus to change its fate and adopt another one. This process can be induced either by a direct exposure of cells to a combination of specific factors or by reconstructing an embryo after the introduction of a cell nucleus into an enucleated oocyte. While the former approach has shown its compatibility with the production of pluripotent cells, only the later, also referred to as cloning, has resulted in a full reprogramming of nuclear functions into live adults. This demonstrates that genome-contained and time-dependent controlled sequences of pre-determined events can be made fully functionally reversible. Recent results obtained from different laboratories including our own lab have identified two key periods for the resetting of the functional activities of a donor nucleus. The first period is bound to nuclear de-differentiation and involves not only cell cycle related nuclear reorganization but also nuclear features such as the peculiar distribution of centromeric and pericentric heterochromatin of the embryonic one cell stage. This period is amenable to transient chromatin manipulation which can markedly improve developmental rates to the early blastocyst stage while keeping intact the potential of its inner cell mass cells to be grown in vitro into fully functional embryonic stem cells similar to those obtained from normal embryos. The second period is related to the functional interactions established between the embryonic and the extraembryonic lineages during blastocyst differentiation and implantation. This period has a major impact on later developmental processes including postnatal life, this mainly through placental dysfunctions related to epigenetic defects. Although the in vitro derivation of stem cell lines from the reprogrammed trophoblast or epiblast lineages is not affected, some differences are observed in term of cell proliferation and pattern of gene expression with their normal counterparts obtained from fertilized blastocysts. Taken together, these data suggests that the epigenetic errors associated with the reprogramming process induced after nuclear transfer are becoming only partially reversible in vitro between the two above defined embryonic periods. This differential situation offers a mean for analyzing the mechanisms associated with the resetting of a pluripotent-like state and for comparing the stability of cell lines derived from a same batch of cultured somatic cells used either as a source of nuclei in cloning experiments or transfected with transcription factors under conditions compatible with the induction of plutipotency.
Mots-clés : CELL LINE
Type de document :
Communication dans un congrès
Liste complète des métadonnées
Déposant : Migration Prodinra <>
Soumis le : jeudi 4 juin 2020 - 02:27:51
Dernière modification le : vendredi 12 juin 2020 - 10:43:26


  • HAL Id : hal-02757789, version 1
  • PRODINRA : 38312
  • WOS : 000266729800030



Jean Paul Renard, Alice Jouneau, Nathalie Beaujean. Reprogramming somatic nuclei into embryonic nulei through nuclear transfer and the stem cell potential of the derived cell lines. 8. Annual Meeting of the French Society of Cell and Gene Therapy, Jun 2009, Paris, France. ⟨hal-02757789⟩



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