Eight genes are enough to turn mouse stem cells into oocytes

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Enough eight genes to make proteins that control genes capable of converting mouse stem cells directly into oocyte-like cells that mature and can even be fertilized as eggs.

This finding, which is published today in «Nature», in addition to providing new insights into the mechanisms of egg development, it may be an important step for reproductive medicine, especially in mitochondrial replacement therapies, in which parts of the oocytes are replaced to prevent mothers from transmitting to their children diseases related to mitochondria.

Stored in the body until they mature and become eggs ready for fertilization, oocytes represent the first step in creating new human life.

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

The authors of the research write that oocytes and their cytoplasm are so extraordinary that they replace the nucleus that contains DNA From one oocyte to that of any other cell in the body, a process called somatic cell nuclear transfer, can produce new life, as was demonstrated with the famous Dolly the sheep.

Therefore, understanding oocyte processes and their development is important both for advancing reproductive medicine and for better understanding how life propagates, but knowledge of the many genes that orchestrate oocyte development is very important. little advanced.

By analyzing the development of mouse oocytes, researchers led by Katsuhiko Hayashi, from the Kyushu University (Japan), have identified eight genes that are not only necessary for the growth of oocytes, but can also convert mouse stem cells into oocyte-like cells.

It is important that stem cells can be converted directly into oocyte-like cells without following the same sequence of steps that occur naturally

In collaboration with researchers from RIKEN Institute, Hayashi’s group discovered that both mouse embryonic stem cells and induced pluripotent stem cells (iPS), which can be created from adult cells, are constantly converted into oocyte-like cells when forced to produce the set of eight transcription factors, with only four factors being sufficient in some cases, although with worse reproducibility.

“It is important that stem cells can be converted directly into oocyte-like cells without following the same sequence of steps that occur naturally,” says Hayashi.

The cytoplasm of oocytes is an invaluable resource in reproductive biology and medicine

In addition, when grown in the presence of other cells that are commonly found around oocytes, these oocyte-like cells developed structures similar to mature eggs, but with a abnormal chromosomal structure. Despite this, mature oocyte-like cells could be fertilized in vitro and exhibit early development, with some even progressing to an eight-cell stage.

Although they recognize that the modified nuclei of these cells may not be viable in the long term, this is not a problem for applications that primarily need the cytoplasm of oocytes, such as for reproductive biology studies and for treatments such as mitochondrial replacement therapy. .

“The cytoplasm of oocytes is an invaluable resource in reproductive medicine and biology, and this method could provide an innovative tool to produce large quantities without any invasive procedures,” Hayashi concludes.

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