Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200120, China.
Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Protein Cell. 2023 May 8;14(5):337-349. doi: 10.1093/procel/pwac041.
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.
人类多能干细胞为体外研究人类胚胎发生提供了取之不尽的模型。最近的研究提供了多种模型,可通过不同的多能干细胞或体细胞核重编程中间产物的自我组织来产生类囊胚。然而,是否可以从其他细胞类型产生类囊胚,或者它们是否可以在体外再现植入后发育尚不清楚。在这里,我们开发了一种从具有原始到幼稚转化过程的上皮细胞、滋养外胚层和原始内胚层特征的异质中间产物中生成人类类囊胚的策略,这些类囊胚在形态结构、细胞谱系组成、转录组和谱系分化潜能上与天然囊胚相似。此外,当这些类囊胚在体外 3D 培养系统中进一步培养时,它们反映了许多人类植入前和原肠胚期发育的特征。总之,我们的研究提供了一种生成人类类囊胚的替代策略,并通过体外模拟植入前和植入后发育为人类早期胚胎发生提供了新的见解。