Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
Cell. 2024 May 23;187(11):2838-2854.e17. doi: 10.1016/j.cell.2024.04.029. Epub 2024 May 13.
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.
对人类的回溯谱系重建预测，体内明显的克隆失衡可以追溯到 2 细胞期胚胎。然而，胚胎中是否以及如何出现这种克隆不对称性尚不清楚。在这里，我们使用活体成像、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 细胞期胚胎的卵裂球对上胚层（体）、下胚层（卵黄囊）和滋养外胚层（胎盘）的贡献。我们发现，大多数上胚层细胞仅来自胚胎的一个卵裂球。我们观察到，只有一个到三个细胞在 8-16 细胞阶段过渡时被内化。此外，这些内化细胞更经常来自于 2 细胞阶段第一次分裂的细胞。我们提出，细胞分裂动力学和早期胚胎中的细胞内化瓶颈在未来人类身体的克隆组成中建立了不对称性。
