Retrospective lineage reconstruction of humans predicts that dramatic clonal imbalances in the body can be traced to the 2-cell stage embryo. However, whether and how such clonal asymmetries arise in the embryo is unclear. Here, we performed prospective lineage tracing of human embryos using live imaging, non-invasive cell labeling, and computational predictions to determine the contribution of each 2-cell stage blastomere to the epiblast (body), hypoblast (yolk sac), and trophectoderm (placenta). We show that the majority of epiblast cells originate from only one blastomere of the 2-cell stage embryo. We observe that only one to three cells become internalized at the 8-to-16-cell stage transition. Moreover, these internalized cells are more frequently derived from the first cell to divide at the 2-cell stage. We propose that cell division dynamics and a cell internalization bottleneck in the early embryo establish asymmetry in the clonal composition of the future human body.

中文翻译：

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前两个卵裂球对人类胚胎的贡献不均


人类的回顾性谱系重建预测，体内剧烈的克隆失衡可以追溯到 2 细胞阶段胚胎。然而，这种克隆不对称是否以及如何在胚胎中出现尚不清楚。在这里，我们使用实时成像、非侵入性细胞标记和计算预测对人类胚胎进行前瞻性谱系追踪，以确定每个 2 细胞阶段卵裂球对外胚层（体）、下胚层（卵黄囊）和滋养外胚层的贡献。胎盘）。我们发现大多数外胚层细胞仅起源于 2 细胞阶段胚胎的一个卵裂球。我们观察到，在 8 到 16 细胞阶段转变时，只有 1 到 3 个细胞被内化。此外，这些内化细胞更频繁地源自在2细胞阶段分裂的第一个细胞。我们认为早期胚胎中的细胞分裂动力学和细胞内化瓶颈在未来人体的克隆组成中建立了不对称性。