Researchers in China, Bangladesh, and United Kingdom have described a transgene-free method to convert pluripotent stem-cells into the more juvenile 8-cell totipotent embryo-like cells, and demonstrated the latter’s ability to create early embryonic cells. The findings are significant for advancing organ regeneration and synthetic biology.
“Totipotent 8-cell stage embryo-like cells recreate the embryonic state of a fertilized egg after only 3 divisions. Compared to the reported pluripotent stem cells, these cells can not only differentiate into placental tissue, but also potentially develop into more mature organs, bringing good news to the millions of patients in need of organ transplants around the world, " says corresponding authors of the paper, Professor Miguel A. Esteban, Dr. Md. Abdul Mazid and Dr. Li Wenjuan from the Chinese Academy of Sciences.
Using BGI Group’s advanced single-cell sequencing technologies, the team converted pluripotent stem cells—considered an “adult” version of early embryonic cells—into the more juvenile version of cells that capture human zygotic genome activation and retain all lineage with developmental potential. While the technology to convert pluripotent stem cells into inner cell mass-like cells inside the blastocyst has existed for some time, this study is the first time researchers established methods to convert pluripotent stem cells to a bona fide earlier stage in the cycle of human development that matches the 8-cell embryo.
Such cells could be used to regenerate human organs that have become diseased or to generate artificial blastocysts or blastoids. They could also be useful for studying human embryonic development, treating early developmental-related diseases, and preventing pregnancy loss.
Among other experiments, the group sorted the cells and injected them into a mouse to undergo further development. The cells were then analyzed using BGI’s single-cell genomic analysis, which helped the team identify and isolate the target 8-cell embryo-like cells and demonstrate their ‘totipotent’ ability to create the cells involved in generating placenta in vivo.
The research, published recently in Nature, could eventually enable individualized organ regeneration, eliminating the need to identify matching donors. It could also provide a new in vitro research system for basic research on early embryonic development, helping advance understanding of the relationship between early embryonic development and disease occurrence.