Eight genes are enough to turn mouse stem cells into oocyte-like cells

In a new study published in the journal Nature, researchers in Japan report that activating just eight genes for the release of gene-controlling proteins is enough to convert mouse stem cells into mature oocyte-like cells and even fertilize as egg cells.

As well as providing new insights into egg cell development methods, the research could lead to a simple pathway to create highly specialized products that are unique to oocytes for use in reproductive biology and medicine.

Stored in the body until they mature into egg cells ready for fertilization, oocytes represent the first step in the creation of new human life.

Oocytes are very special because of their ability to produce more than two hundred different types of cells that are needed to form an individual, and one key method is the ability this is the complex mixture of substances within the cytoplasm similar to fluid filling the cells.

The magnificence of oocytes and their cytoplasm that can replace an oocyte’s DNA nucleus with a body cell – a process known as somatic cell nuclear migration – has produced a new life, as it famously proved by Dolly the sheep.

Thus, a basic understanding of oocytes and their development is important for advancing reproductive therapy and better grasp of how life extends, but knowledge of the many species that leading oocyte development remains far from complete.

Analyzing the development of oocytes from mice, researchers led by Katsuhiko Hayashi, a professor at the Faculty of Medical Sciences of Kyushu University, have now identified eight genes for gene-stimulating proteins called transcription factors which is not only essential for oocyte growth but also can adapt directly. mouse gases into oocyte-like cells.

“I was initially skeptical of seeing mouse stem cells so quickly and easily in the form of oocytes based on the incorporation of just a handful of factors, but experiments have again confirmed that it was true, ”said Nobuhiko Hamazaki, the study’s first author reporting on their findings and an assistant professor at Kyushu University at the time of the research. “I was surprised to learn that eight transcription factors could lead to such huge changes. “

Working in collaboration with researchers at RIKEN, Hayashi’s group found that both mouse transducer stem cells and stimulated stem cells (iPS) – which can be formed from adult body cells – are constantly being modified. as oocyte-like cells when taken to eight sets of transcription factors, with only four factors sufficient in some cases but with worse reproduction.

“These stem cells can be transformed directly into oocyte-like cells without following the same series of naturally occurring steps,” says Hayashi.

When grown in the presence of other cells commonly found around oocytes, the oocyte-like cells develop mature egg-like structures but with an unusual chromosome structure. Nevertheless, the oocyte-like mature cells could be fertilized in vitro and exhibit early development, with some even progressing to the eight-cell stage.

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

“Cytoplasm from oocytes is a valuable resource in reproductive biology and medicine, and this method could provide a new tool for extracting much of it without any invasive methods,” says Hayashi “While the processes may be much more complex for humans, these initial results in mice are very promising. ”

Presented by Kyushu University