Scientists have been able reprogram embryonic stem cells to expand their potential

Researchers from the University of California – Berkeley have created the technique of reprogramming of mouse embryonic stem cells to totipotent cells, such as those that are in the zygote. The study were published Jan. 12, 2017 in the journal Science.

Pluripotent stem cells (PSC) can differentiate into most tissues of the body, but they cannot turn into cells extra-embryonic tissue – placenta or yolk sac, such as the one-celled fertilized egg or two-celled zygote.

Groups of scientists under the guidance of Prof. Lin He have found that by blocking a specific microRNA, PSC can differentiate into cells extra-embryonic tissue, which opens up new prospects for the use of induced pluripotent stem cells (iPS cells) in regenerative medicine.

These “totipotent-like” stem cells are able to generate not only all cell types within a developing embryo, but also cell types that facilitate nutrient exchange between the embryo and the mother.

New lines of stem cells researchers have created will help understand the molecular processes in the early embryo at the initial stages of development. Finally, this research may increase the amount of tissue types derived from stem cells.

Fertilized egg has the full potential of producing all types of cells required for the formation of the fetus and its extra-embryonic tissues. This property of totipotency is observed only in the very early stages of embryogenesis.

In contrast, the majority of embryonic and induced pluripotent stem cells have limited potential for development. They can only create tissue cells of the embryo.

Embryonic stem cells (ESCs) derived from the 3.5-day-old mouse embryos or 5.5-day-old human embryos, in the last few decades cause attention of scientists. ESC allow the identification of the genetic switches that control the development of the specialized embryonic tissues. Also, these stem cells have the invaluable potential to recover precious organ tissues, which are not capable of regeneration, such as the pancreas cells in diabetes or cardiac muscles in congestive heart failure. Furthermore, ESCs allow studying the early stages of genetic diseases.

Alternatively embryo cells, scientists use iPS obtained from mature somatic cells treated with a cocktail of transcription factors, causing them to regress acquiring properties that are similar to ESCs. However, neither ES nor iPS cells, have no properties of a fertilized egg that is capable to produce both embryonic and extra-embryonic tissues.

MicroRNAs are small non-coding RNAs that do not involved in protein translation. They regulate the gene expression process. Lin He and her colleagues found that a microRNA known as miR-34a, inhibits the production extra-embryonic tissue in iPS cells and ESCs.

When this microRNA was genetically removed, both embryonic and induced pluripotent stem cells could differentiate into embryonic cells, placenta and yolk sac. In experiments about 20% of ESCs deprived of miR-34a, demonstrated the exhibited expanded fate potential.

“What is quite amazing is that manipulating just a single microRNA was able to greatly expand cell fate decisions of embryonic stem cells,” said Lin He. “This finding not only identifies a new mechanism that regulates totipotent stem cells, but also reveals the importance of non-coding RNAs in stem cell fate.”

In this study, a group of He also discovered an unexpected link between miR-34a and a specific class of mouse retrotransposons. For a long time was thought that “junk DNA” retrotransposons are pieces of ancient foreign DNA that make up a significant part of the mammalian genome. For decades, biologists believed that retrotransposons have no role in normal development, but He’s findings suggest that they may be closely tied to the decision-making of early embryos.