Modelling human blastocysts by reprogramming fibroblasts into iBlastoids

Xiaodong Liu, Jia Ping Tan, Jan Schröder, Asma Aberkane, John F. Ouyang, Monika Mohenska, Sue Mei Lim, Yu B.Y. Sun, Joseph Chen, Guizhi Sun, Yichen Zhou, Daniel Poppe, Ryan Lister, Amander T. Clark, Owen J.L. Rackham, Jennifer Zenker, Jose M. Polo

Research output: Contribution to journalArticleResearchpeer-review

84 Citations (Scopus)

Abstract

Human pluripotent and trophoblast stem cells have been essential alternatives to blastocysts for understanding early human development1–4. However, these simple culture systems lack the complexity to adequately model the spatiotemporal cellular and molecular dynamics that occur during early embryonic development. Here we describe the reprogramming of fibroblasts into in vitro three-dimensional models of the human blastocyst, termed iBlastoids. Characterization of iBlastoids shows that they model the overall architecture of blastocysts, presenting an inner cell mass-like structure, with epiblast- and primitive endoderm-like cells, a blastocoel-like cavity and a trophectoderm-like outer layer of cells. Single-cell transcriptomics further confirmed the presence of epiblast-, primitive endoderm-, and trophectoderm-like cells. Moreover, iBlastoids can give rise to pluripotent and trophoblast stem cells and are capable of modelling, in vitro, several aspects of the early stage of implantation. In summary, we have developed a scalable and tractable system to model human blastocyst biology; we envision that this will facilitate the study of early human development and the effects of gene mutations and toxins during early embryogenesis, as well as aiding in the development of new therapies associated with in vitro fertilization.

Original languageEnglish
Pages (from-to)627-632
Number of pages6
JournalNature
Volume591
Issue number7851
DOIs
Publication statusPublished - 25 Mar 2021

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