Mammalian embryos sequentially differentiate into trophectoderm and an inner cell mass, the latter of which differentiates into primitive endoderm and epiblast. Trophoblast stem (TS), extraembryonic endoderm (XEN) and embryonic stem (ES) cells derived from these three lineages can self-assemble into synthetic embryos, but the mechanisms remain unknown. Here, we show that a stem cell-specific cadherin code drives synthetic embryogenesis. The XEN cell cadherin code enables XEN cell sorting into a layer below ES cells, recapitulating the sorting of epiblast and primitive endoderm before implantation. The TS cell cadherin code enables TS cell sorting above ES cells, resembling extraembryonic ectoderm clustering above epiblast following implantation. Whereas differential cadherin expression drives initial cell sorting, cortical tension consolidates tissue organization. By optimizing cadherin code expression in different stem cell lines, we tripled the frequency of correctly formed synthetic embryos. Thus, by exploiting cadherin codes from different stages of development, lineage-specific stem cells bypass the preimplantation structure to directly assemble a postimplantation embryo.

哺乳动物胚胎依次分化为滋养外胚层和内细胞团，后者分化为原始内胚层和外胚层。来自这三个谱系的滋养层干细胞（TS）、胚外内胚层细胞（XEN）和胚胎干细胞（ES）可以自组装成合成胚胎，但其机制仍不清楚。在这里，我们展示了干细胞特异性钙粘蛋白代码驱动合成胚胎发生。 XEN 细胞钙粘蛋白代码使 XEN 细胞能够分类到 ES 细胞下方的一层，重现植入前外胚层和原始内胚层的分类。 TS 细胞钙粘蛋白代码使 TS 细胞能够在 ES 细胞上方进行分类，类似于植入后胚胎外外胚层在外胚层上方聚集。钙粘蛋白表达差异驱动初始细胞分类，而皮质张力则巩固组织组织。通过优化不同干细胞系中钙粘蛋白代码的表达，我们将正确形成的合成胚胎的频率增加了两倍。因此，通过利用来自不同发育阶段的钙粘蛋白代码，谱系特异性干细胞绕过植入前结构直接组装植入后胚胎。