美国加州理工学院Magdalena Zernicka-Goetz团队近期取得重要工作进展。他们研究揭示了干细胞来源的合成胚胎通过利用钙粘蛋白和皮层张力自我组装。这一研究成果2022年9月13日在线发表于《自然- 细胞生物学》杂志上。

研究人员发现干细胞特异性钙粘蛋白驱动合成胚胎发生。XEN细胞钙粘蛋白使XEN细胞分选到ES细胞下方的一层，再现了植入前外胚层和原始内胚层的分选过程。TS细胞钙粘蛋白使TS细胞能够在ES细胞上方分选，类似于植入后的胚胎外胚层聚集在外胚层之上。虽然差异钙粘蛋白表达驱动初始细胞分类，但皮质张力巩固组织结构。通过优化不同干细胞系中的钙粘蛋白表达，研究人员将正确形成的合成胚胎的频率提高了两倍。因此，通过利用来自不同发育阶段的钙粘蛋白，谱系特异性干细胞绕过着床前结构直接组装植入后胚胎。

据介绍，哺乳动物胚胎依次分化为滋养外胚层和内细胞团，内细胞团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（XEN）和胚胎干细胞（ES）可以自我组装成合成胚胎，但其机制仍然未知。

附：英文原文

Title: Stem cell-derived synthetic embryos self-assemble by exploiting cadherin codes and cortical tension

Author: Bao, Min, Cornwall-Scoones, Jake, Sanchez-Vasquez, Estefania, Chen, Dong-Yuan, De Jonghe, Joachim, Shadkhoo, Shahriar, Hollfelder, Florian, Thomson, Matt, Glover, David M., Zernicka-Goetz, Magdalena

Issue&Volume: 2022-09-13

Abstract: 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.

DOI: 10.1038/s41556-022-00984-y

Source: https://www.nature.com/articles/s41556-022-00984-y