Efficient generation of germline chimeras in a non-rodent species using rabbit induced pluripotent stem cells
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.
Article Details
Authors (19)
Hong-Thu Pham
Florence Perold
Yannicke Pijoff
Nathalie Doerflinger
Sylvie Rival-Gervier
Maëlle Givelet
Anaïs Moulin
Manon Ressaire
Emilie Da Silva Fernandes
Valeska Bidault
Luc Jouneau
Véronique Duranthon
Florence Wianny
Bertrand Pain
Ingrid Plotton
Centre hospitalier universitaire de Lyon, laboratoire de biochimie et biologie moléculaire, Université Lyon 1
Thierry Joly
Marielle Afanassieff
Pierre Savatier
Nathalie Beaujean