A study reveals that the first two blastomeres in a human embryo contribute unequally to the development of the embryo. Using live imaging and lineage tracing, researchers found that the majority of the epiblast (future body) cells originate from one of the two 2-cell stage blastomeres. The first blastomere to divide at the 2-cell stage generates more asymmetric divisions at the 8-cell stage, leading to a small number of founding epiblast cells before implantation. This process creates a clonal imbalance in the embryo, with the majority of the epiblast cells coming from one blastomere. The study also shows that the number and timing of internalized cells influence the clonal composition of the future body. The findings suggest that early cell division dynamics and a cell internalization bottleneck in the embryo establish asymmetry in the clonal composition of the human body. The study highlights the importance of understanding the early stages of embryonic development and the role of asymmetric cell divisions in shaping the future body. The results have implications for understanding human development and potential applications in reproductive medicine.A study reveals that the first two blastomeres in a human embryo contribute unequally to the development of the embryo. Using live imaging and lineage tracing, researchers found that the majority of the epiblast (future body) cells originate from one of the two 2-cell stage blastomeres. The first blastomere to divide at the 2-cell stage generates more asymmetric divisions at the 8-cell stage, leading to a small number of founding epiblast cells before implantation. This process creates a clonal imbalance in the embryo, with the majority of the epiblast cells coming from one blastomere. The study also shows that the number and timing of internalized cells influence the clonal composition of the future body. The findings suggest that early cell division dynamics and a cell internalization bottleneck in the embryo establish asymmetry in the clonal composition of the human body. The study highlights the importance of understanding the early stages of embryonic development and the role of asymmetric cell divisions in shaping the future body. The results have implications for understanding human development and potential applications in reproductive medicine.