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Efficient generation of germline chimeras in a non-rodent species using rabbit induced pluripotent stem cells

Author

Listed:
  • Hong-Thu Pham

    (INRAE USC 1361)

  • Florence Perold

    (INRAE USC 1361)

  • Yannicke Pijoff

    (INRAE USC 1361)

  • Nathalie Doerflinger

    (INRAE USC 1361)

  • Sylvie Rival-Gervier

    (INRAE USC 1361)

  • Maëlle Givelet

    (INRAE USC 1361)

  • Anaïs Moulin

    (INRAE USC 1361)

  • Manon Ressaire

    (INRAE USC 1361)

  • Emilie Silva Fernandes

    (INRAE USC 1361)

  • Valeska Bidault

    (INRAE USC 1361
    Hospices Civils de Lyon)

  • Luc Jouneau

    (BREED
    BREED)

  • Véronique Duranthon

    (BREED
    BREED)

  • Florence Wianny

    (INRAE USC 1361)

  • Bertrand Pain

    (INRAE USC 1361)

  • Ingrid Plotton

    (INRAE USC 1361
    Hospices Civils de Lyon)

  • Thierry Joly

    (ISARA-Lyon
    UPSP ICE)

  • Marielle Afanassieff

    (INRAE USC 1361
    Stem Cell and Brain Research Institute U1208)

  • Pierre Savatier

    (INRAE USC 1361
    Stem Cell and Brain Research Institute U1208)

  • Nathalie Beaujean

    (INRAE USC 1361)

Abstract

Pluripotent stem cells have long been used to produce knockout mice via germline chimera technology. However, aside from the rat, this approach has not been successfully applied to other mammals. Here, we demonstrate that rabbit induced pluripotent stem cells (iPSCs) can be reprogrammed using KLF2, ERAS and PRMT6, enabling them to efficiently colonize embryos. These chimeric embryos can develop into fetuses and newborn rabbits, with iPSCs contributing up to 100 % to certain organs. Notably, female rabbits generated through this method are healthy and transmit the iPSC genome to their offspring with a high efficiency, demonstrating germline chimerism. This advancement establishes a foundation for developing rabbit models of human disease with complex genetic traits.

Suggested Citation

  • Hong-Thu Pham & Florence Perold & Yannicke Pijoff & Nathalie Doerflinger & Sylvie Rival-Gervier & Maëlle Givelet & Anaïs Moulin & Manon Ressaire & Emilie Silva Fernandes & Valeska Bidault & Luc Jounea, 2025. "Efficient generation of germline chimeras in a non-rodent species using rabbit induced pluripotent stem cells," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60314-2
    DOI: 10.1038/s41467-025-60314-2
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