The first two blastomeres contribute unequally to the human embryo

“…It is postulated that even small asymmetries between the blastomeres at the 2-cell stage can be amplified with time and translate to different cell fate (Chen et al, 2018) . This is consistent with the observations that asymmetries in the timing of division in 2-cell embryos could be linked to the asymmetries that contribute to the ICM during the 8- to 16-cell stage division (Junyent et al, 2024) . Our current observations point towards the influence of size differences between 2-cell blastomeres upon division timing.…”

“…Precisely how any change in cell cycle synchronicity could impact upon CHD remains to be determined, but there is some evidence from lower animals such as sea urchin and Drosophila that it can regulate embryonic patterning and cell fate decisions (reviewed in [ 31 ]). Furthermore, recent evidence has shown that the lineages of the blastomeres of the 2-cell human embryo contribute unequally to the inner cell mass of the blastocyst, and that those cells thus incorporated into the embryo proper are more likely to arise from the first cell to divide at the second cell cycle [ 24 ]. Differences in cell fate also exist between the four blastomeres of the 2-cell and 4-cell mouse embryos [ 32 , 33 ] which may be related to unequal distribution of maternal mRNA [ 32 ].…”

“…For decades, it was thought that the blastomeres of mouse and human embryos are equivalent to each other in their developmental properties until reaching differential positions within the embryo at the 16-cell stage. However, the advent of new technologies to track individual cells in living embryos to determine their developmental fate and potential, and to examine the patterns of gene expression in single cells, has shown that blastomeres can become different from each other at earlier stages of development 12,19,21,35,56,57,86 . Moreover, only one sister blastomere appears to be truly totipotent in the majority of 2-cell mouse embryos when sister blastomeres are separated from each other 7,10 .…”

“…We and others previously showed that the developmental potential and subsequent fate of 2-cell stage sister blastomeres are unequal 7–12,19,56 . Specifically, separated sister blastomeres of the 2-cell mouse embryo show discordance in their ability to give rise to a viable embryo and show variation in epiblast size 10 , with one blastomere giving rise to more epiblast cells than its sister (Extended Data Fig.…”