Tetraploid embryonic stem cells can contribute to the development of chimeric fetuses and chimeric extraembryonic tissues

Abstract

Our study examined the in vivo chimeric and survival capacities of chimeras created by injecting tetraploid embryonic stem cells (ESCs) expressing green fluorescent protein (GFP) into diploid embryos. At 3.5 days post-coitum (dpc) and 4.5 dpc, the tetraploid ESCs were able to contribute to the inner cell mass (ICM) just as diploid ESCs tagged with GFP. At 6.5 dpc, 8.0 dpc and 10.5 dpc, the tetraploid ESCs manifested in the same location as the diploid ESCs. The GFP cells in the extraembryonic tissues and fetuses of tetraploid ESC chimeras were tetraploid as determined by fluorescence activated cell sorting (FACS). Furthermore, tetraploid ESCs contributed to the development of the placenta, embryolemma and umbilical cord at 13.5 dpc and 16.5 dpc; however, very less GFP cells were found in the fetuses of tetraploid ESC chimeras. We further found that the proliferation of tetraploid ESCs was slower than that of diploid ESCs. In addition, the relative mRNA expression in the three germ layers and the trophoblast was abnormal in the EBs of tetraploid ESCs compared with diploid ESCs. In short, slower proliferation and abnormal differentiation potential of tetraploid ESCs might be two of the reasons for their poor survival and chimeric capacities.

Paraffin-embedded vertical sections of mouse embryonic stem cells

“…1B right column arrowheads). Previous studies reported that horizontal morphology of colonies was similar between diploid and tetraploid ESCs as assessed using inverted microscopes [ 2 , 4 , 11 ], and this vertical analysis strongly supported the similarity. Here, we showed the histological utility of the new method of vertically sectioning stereoscopic cell colonies, such as mouse embryonic stem cells, for the first time.…”

A Survey of Essential Genome Stability Genes Reveals That Replication Stress Mitigation Is Critical for Peri-Implantation Embryogenesis

“…chromosomal instability in preimplantation cells (Paim and FitzHarris, 2019) chimeric mouse embryos with a mixture of diploid and tetraploid cells will develop through preimplantation before dying during peri-implantation (Horii et al, 2015). Notably, tetraploid sensitivity in vivo appears to be specific to the epiblast as embryos with tetraploid trophoblast cells and diploid epiblast cells can generate live pups (Wen et al, 2017). Mouse embryos containing a mixture of diploid and aneuploid cells will also develop to peri-implantation before the aneuploid cells are specifically depleted in the epiblast through apoptosis (Bolton et al, 2016).…”

Hyper-polyploid embryos survive after implantation in mice

“…Other reports have shown that the more polyploidization, the less the number of the inner cell mass in blastocysts (Liu et al, 2004;Lei et al, 2009). Tetraploid embryonic stem cells established from mouse tetraploid blastocysts have shown increment in apoptosis, and decrement of proliferation rate and meiosis-related gene expression (Horii et al, 2015;Imai et al, 2015;Wen et al, 2017).…”