Frade, JoãoNakagawa, ShomaCortes, PaolaDi Vicino, UmbertoRomo Saladrigas, Neus, 1982-Lluis Vinas, FredericCosma, Maria Pia, 1970-2020-04-072020-04-072019Frade J, Nakagawa S, Cortes P, di Vicino U, Romo N, Lluis F, Cosma MP. Controlled ploidy reduction of pluripotent 4n cells generates 2n cells during mouse embryo development. Sci Adv. 2019; 5(10):eaax4199. DOI: 10.1126/sciadv.aax41992375-2548http://hdl.handle.net/10230/44179Cells with high ploidy content are common in mammalian extraembryonic and adult tissues. Cell-to-cell fusion generates polyploid cells during mammalian development and tissue regeneration. However, whether increased ploidy can be occasionally tolerated in embryonic lineages still remains largely unknown. Here, we show that pluripotent, fusion-derived tetraploid cells, when injected in a recipient mouse blastocyst, can generate diploid cells upon ploidy reduction. The generated diploid cells form part of the adult tissues in mouse chimeras. Parental chromosomes in pluripotent tetraploid cells are segregated through tripolar mitosis both randomly and nonrandomly and without aneuploidy. Tetraploid-derived diploid cells show a differentiated phenotype. Overall, we discovered an unexpected process of controlled genome reduction in pluripotent tetraploid cells. This mechanism can ultimately generate diploid cells during mouse embryo development and should also be considered for cell fusion-mediated tissue regeneration approaches.application/pdfeng© 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).info:eu-repo/semantics/articlehttp://dx.doi.org/10.1126/sciadv.aax4199info:eu-repo/semantics/openAccess