New tool for reproductive medicine

Researchers at Kyushu University in Japan directly transformed stem cells into oocyte-like cells using a set of just eight transcription factors.

December 17, 2020 10:22

Researchers in Japan have found that activating only eight genes to produce genes that control genes is enough to convert stem cells directly into oocyte-like cells that mature and can even be fertilized as eggs, according to the journal Nature. “. This surprisingly simple method could provide a new tool to produce specialized cytoplasm for reproductive medicine.

In addition to providing new perspectives on the mechanisms of egg development, research can lead to a simple way to generate highly specialized substances, unique to oocytes, for use in reproductive medicine and biology.

Stored in the body until they mature into eggs ready for fertilization, oocytes are the first step in creating a new human life.

Oocytes are extremely unique due to their ability to produce more than two hundred highly differentiated cell types needed to create an individual person, and a key to this ability is the complex mixture of substances in the fluid cytoplasm that fills cells. researchers.

Their oocytes and cytoplasm are so extraordinary that the replacement of the nucleus containing the DNA of an oocyte with that of a cell in the body, a process called nuclear somatic cell transfer, can bring a new life, as demonstrated by the famous sheep Dolly.

Therefore, a fundamental understanding of oocytes and their development is important both to advance reproductive medicine and to better understand how life propagates, but knowledge of many genes that orchestrate oocyte development is still far from complete.

Analyzing the development of oocytes from experimental models, researchers led by Katsuhiko Hayashi, a professor at Kyushu University School of Medical Sciences, have now identified eight genes for gene-triggering proteins, known as transcription factors, that are not only necessary for oocyte growth, but it can also directly convert stem cells into oocyte-like cells.

“I was initially completely distrustful to see that stem cells took the shape of oocytes so quickly and easily based on the introduction of only a handful of factors, but repeated experiments showed that it was true,” says Nobuhiko Hamazaki, the study’s first author. reported on the results and assistant professor at Kyushu University at the time of the research. Finding out that eight transcription factors could lead to such large changes was quite surprising. “

Working with RIKEN researchers, Hayashi’s group discovered this both embryonic stem cells and induced pluripotent stem cells (iPS), which can be created from adult body cells, are constantly transformed into oocyte-like cells when forced to produce the whole. out of eight transcription factors, only four factors being sufficient in some cases, although with lower reproducibility.

“It simply came to our notice then stem cells can be converted directly into oocyte-like cells without following the same sequence of steps that take place naturally “, Hayashi emphasizes.

When cultured in the presence of other cells that are generally found around oocytes, oocyte-like cells have developed structures similar to mature eggs, but with an abnormal chromosomal structure. Despite this, oocyte-like mature cells could be fertilized in vitro and show early development, some even progressing to an eight-cell stage.

Although modified oocyte-like cell nuclei may not be usable in the long term, this is not a problem for applications that primarily require oocyte cytoplasm, such as reproductive biology studies and treatments such as replacement therapy. . mitochondria, in which parts of the oocytes are replaced to prevent mothers from transmitting mitochondrial diseases to their children.

“Oocyte cytoplasm is an invaluable resource in reproductive medicine and biology, and this method could provide a new tool to produce large quantities without any invasive procedure,” says Hayashi. While the processes may be much more complex for humans, these initial results in mice are very promising. “