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

Hong-Thu Pham, Florence Perold, Yannicke Pijoff, Nathalie Doerflinger, Sylvie Rival-Gervier, Maëlle Givelet, Anaïs Moulin, Manon Ressaire, Emilie Silva Fernandes, Valeska Bidault, Luc Jouneau, Véronique Duranthon, Florence Wianny, Bertrand Pain, Ingrid Plotton, Thierry Joly, Marielle Afanassieff (), Pierre Savatier () and Nathalie Beaujean ()
Additional contact information
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
Luc Jouneau: BREED
Véronique Duranthon: BREED
Florence Wianny: INRAE USC 1361
Bertrand Pain: INRAE USC 1361
Ingrid Plotton: INRAE USC 1361
Thierry Joly: ISARA-Lyon
Marielle Afanassieff: INRAE USC 1361
Pierre Savatier: INRAE USC 1361
Nathalie Beaujean: INRAE USC 1361

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: 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.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60314-2

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DOI: 10.1038/s41467-025-60314-2

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