Efficient generation of germline chimeras in a non-rodent species using rabbit induced pluripotent stem cells
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.
Authors
- Luc Jouneau (ORCID: https://orcid.org/0000-0002-5094-7302)
- Eliana Fernandes (ORCID: https://orcid.org/0000-0003-4083-8353)
- Florence Wianny
- Anaïs Moulin
- V. Bidault (ORCID: https://orcid.org/0000-0002-2163-8455)
- Sylvie Rival‐Gervier (ORCID: https://orcid.org/0000-0001-8266-8095)
- Bertrand Pain (ORCID: https://orcid.org/0000-0002-1210-8444)
- Florence Perold
- Nathalie Beaujean (ORCID: https://orcid.org/0000-0003-0188-9190)
- Nathalie Doerflinger
- Marielle Afanassieff (ORCID: https://orcid.org/0000-0002-6353-6617)
- Véronique Duranthon (ORCID: https://orcid.org/0000-0001-8120-7481)
- Pierre Savatier (ORCID: https://orcid.org/0000-0002-8944-9853)
- Maëlle Givelet
- Ingrid Plotton (ORCID: https://orcid.org/0000-0003-2539-0087)
- Thierry Joly (ORCID: https://orcid.org/0000-0002-4002-7748)
- Yannicke Pijoff
- Hong-Thu Pham
- Manon Ressaire
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Inserm (FR)
- École Nationale Vétérinaire d'Alfort (FR)
- Lyon College (US)
- Université de Versailles Saint-Quentin-en-Yvelines (FR)
- Université Paris-Saclay (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Centre de Recherche en Neurosciences de Lyon (FR)
- Hospices Civils de Lyon (FR)
- VetAgro Sup (FR)
- Institut Cellule Souche et Cerveau (FR)
- Institut Supérieur d'Agriculture Rhône-Alpes (FR)
- Biologie de la Reproduction, Environnement, Epigénétique et Développement (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-06-03
- DOI
- https://doi.org/10.1038/s41467-025-60314-2
- Citations
- 3
- Primary Topic
- Pluripotent Stem Cells Research
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale
- Université de Lyon
- LabEx DEvweCAN
- Samsung Biomedical Research Institute