Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.
Stem Cell Institute Leuven (SCIL), Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Sci Adv. 2019 Oct 16;5(10):eaax4199. doi: 10.1126/sciadv.aax4199. eCollection 2019 Oct.
Cells 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.
高倍体含量的细胞在哺乳动物的胚胎外和成年组织中很常见。细胞融合在哺乳动物的发育和组织再生过程中产生多倍体细胞。然而，胚胎谱系中是否偶尔可以耐受增加的倍性在很大程度上仍然未知。在这里，我们表明，多能性、融合衍生的四倍体细胞，当注射到受体小鼠囊胚中时，可以在倍性降低后产生二倍体细胞。在嵌合体小鼠中，生成的二倍体细胞形成部分成年组织。多潜能四倍体细胞中的亲代染色体通过三极有丝分裂随机和非随机地分离，没有非整倍性。四倍体衍生的二倍体细胞表现出分化的表型。总的来说，我们发现了多潜能四倍体细胞中一种出乎意料的受控基因组减少过程。这种机制可以在小鼠胚胎发育过程中最终产生二倍体细胞，并且在细胞融合介导的组织再生方法中也应该考虑到这一点。
