BGI-Research, the Chinese Academy of Sciences and a group of collaborators, declared the invention of a transgene-free, instantaneous, and manageable method to transform pluripotent stem cells into bona fide 8-cell totipotent embryo-like cells, laying the groundwork for developments in organ regeneration and synthetic biology. The study was published in the journal Nature.
BGI researchers worked with an international group from China, Bangladesh, and the United Kingdom to help transform pluripotent stem cells, or an “adult” version of early embryonic cells, into a more “juvenile” version of cells that obtain human zygotic genome stimulation and maintain all lineages with developmental competence, using BGI’s advanced single-cell sequencing techniques.
These cells could be employed in the future in regenerative medicine to repair sick human organs and decrease the world’s dependence on organ donors. They can also be utilized to make synthetic blastocysts and blastoids. They will also be beneficial in the research of human embryonic development, as well as in the treatment of early developmental problems and the prevention of fetal loss.
While the innovation to transform pluripotent stem cells into inner mass-like cells inside the blastocyst has been around for a while, this is the very first time scientists have defined methodologies to transform pluripotent stem cells to a bona fide earlier stage in the human development process that corresponds to an 8-cell embryo, which will aid in the understanding of early human embryonic development.
The researchers were also able to show that the transformed cells could generate placental cells in vivo for the first time.
Professor Miguel A. Esteban, Dr Md. Abdul Mazid and Dr Li Wenjuan from the Chinese Academy of Sciences and also the corresponding authors of the study commented, “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,” the authors added.
This breakthrough is also a perfect example of the combination of regenerative medicine and single-cell sequencing technology. Through large-scale single-cell multi-omics profiling, the efficient and precise identification of cells or tissues obtained in vitro or in vivo by stem cell technologies will greatly accelerate researches on regenerative medicine.”
Dr Liu Longqi, Study Corresponding Author, BGI-Research
At this phase of development, cells are said to be “totipotent,” indicating they have the ability to produce a variety of early embryonic cells, which thereafter produce the tissues and organs needed for development. The study expands on prior research with pluripotent stem cells at the blastocyst stage, when cells can only produce a limited number of distinct cells and tissues.
The discovery in the research was aided by breakthroughs in single-cell sequencing technology, which BGI Group leads the world in. Its sequencing method and single-cell library sequencing platform provide comprehensive and multi-dimensional single-cell investigation with excellent precision and accuracy at a cheap cost.
To make the 8-cell embryo-like cells, the multinational team used pluripotent stem cells and processed them with a chemical cocktail. These cells were separated and implanted into a mouse for further growth, and then examined using BGI’s single-cell genomic analysis, among other tests.
This cutting-edge method assisted researchers in identifying and isolating the target 8-cell embryo-like cells, as well as demonstrating their “totipotent” potential to generate the cells involved in placenta formation in vivo.
The researchers’ progress could lead to customized organ regeneration being a reality in the future. Finding a suitable donor is usually the only option for patients in need of an organ transplant. The methodology is not without flaws.
If the donor’s serotype is too distinct from the recipient’s, the transplant may fail. A different approach involving gene editing to modify animal organs for transplantation to humans is similarly in its early stages.
This discovery also provides a unique in vitro research platform for basic research on early embryonic development, as well as a tool for the evaluation and treatment of birth abnormalities and other developmental illnesses.
Mazid, Md. A., et al. (2022) Rolling back of human pluripotent stem cells to an 8-cell embryo-like stage. Nature. doi.org/10.1038/s41586-022-04625-0.