Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro. Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates. However, whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown. Here, we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast, trophectoderm, and primitive endoderm signatures of the primed-to-naïve conversion process, which resemble natural blastocysts in morphological architecture, composition of cell lineages, transcriptome, and lineage differentiation potential. In addition, these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system. In summary, our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri- and postimplantation development in vitro.

中文翻译：

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通过 3D 培养从启动到幼稚的过渡中间体产生的胚细胞来模拟人类前胃泌素发育。

人类多能干细胞为体外研究人类胚胎发生提供了一个取之不尽用之不竭的模型。最近的研究提供了多种模型，通过不同多能干细胞或体细胞重编程中间体的自组织来产生人类胚细胞。然而，母细胞是否可以从其他细胞类型产生，或者它们是否可以在体外重演植入后发育尚不清楚。在这里，我们开发了一种策略，从具有外胚层、滋养外胚层和原始内胚层特征的异质中间体生成人类胚泡，这些中间体具有启动到幼稚转化过程的特征，在形态结构、细胞谱系组成、转录组和谱系分化方面类似于天然胚泡潜在的。此外，当在体外 3D 培养系统中进一步培养时，这些胚细胞反映了人类着床前和原肠胚发育前发育的许多特征。总之，我们的研究提供了一种替代策略来生成人类母细胞，并通过体外模拟植入前后发育提供对人类早期胚胎发生的见解。