Modelling human blastocysts by reprogramming fibroblasts into iBlastoids

Autor: Amander T. Clark, Jan Schröder, Daniel Poppe, Joseph Chen, Yu Bo Yang Sun, Ryan Lister, Sue Mei Lim, Jose M. Polo, Jia Ping Tan, Xiaodong Liu, Monika Mohenska, Jennifer Zenker, Owen J. L. Rackham, Guizhi Sun, Yichen Zhou, John F. Ouyang, Asma Aberkane
Rok vydání: 2021
Předmět:
Zdroj: Nature. 591:627-632
ISSN: 1476-4687
0028-0836
DOI: 10.1038/s41586-021-03372-y
Popis: 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. Human fibroblasts are reprogrammed to generate blastocyst-like structures called iBlastoids, which recapitulate aspects of embryo implantation.
Databáze: OpenAIRE
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