Single-cell RNA-sequencing of iBlastoids generated by reprogramming

Here, we report an in vitro model of the human blastocyst by reprogramming fibroblasts, termed iBlastoids. Comprehensive characterization of these iBlastoids demonstrated that they can accurately represent the overall architecture of human blastocysts including an inner cell mass-like structure, marked by classic EPI-associated genes surrounded by an outer layer of cells with key molecular characteristics of the TE and a cavity resembling the blastocoel. Single-cell transcriptomics confirmed the presence of EPI, PE and TE-like cells and unveiled a high correlation between blastocysts and iBlastoids. Finally, iBlastoids are capable of modeling in vitro, several molecular and morphological aspects of blastocyst implantation. In summary, we have developed a scalable and tractable model to study the human blastocyst, and we envision that iBlastoids will facilitate further studies of the molecular and functional processes during early human development.