Modeling human pregastrulation development by 3D culture of blastoids generated from primed-to-naïve transitioning intermediates.

Zhifen TU; Yan BI; Xuehao Zhu; Wenqiang Liu; Jindian HU; Li WU; Tengyan Mao; Jianfeng Zhou; Hanwei Wang; Hong Wang; Shaorong Gao; Yixuan Wang

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Modeling human pregastrulation development by 3D culture of blastoids generated from primed-to-naïve transitioning intermediates.

Author: Zhifen TU ¹ ; Yan BI ¹ ; Xuehao ZHU ¹ ; Wenqiang LIU ² ; Jindian HU ¹ ; Li WU ² ; Tengyan MAO ¹ ; Jianfeng ZHOU ¹ ; Hanwei WANG ¹ ; Hong WANG ¹ ; Shaorong GAO ¹ ; Yixuan WANG ¹
Author Information

1. 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.
2. 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.
Publication Type:Research Support, Non-U.S. Gov't
Keywords: blastoids; naïve conversion; pregastrulation modeling; primed; to; transitioning intermediates
MeSH: Humans; Pluripotent Stem Cells/metabolism*; Embryo, Mammalian/metabolism*; Cell Differentiation; Blastocyst; Cell Lineage; Embryonic Development
From: Protein & Cell 2023;14(5):337-349
CountryChina
Language:English
Abstract: 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.