Eight genes are enough
Biologists have identified genes whose inclusion turns stem cells into eggs
Molecular biologists have identified eight genes, the forced inclusion of which can turn stem cells into full-fledged eggs suitable for procreation. The results of their research were published in the scientific journal Nature (Hamazaki et al., Reconstruction of the oocyte transcriptional network with transcription factors).
"At first I couldn't believe my eyes when I saw how quickly and easily the stem cells of mice became like oocytes after I injected them with only a few stimulators of gene activity. Further experiments, however, confirmed that such serious changes can be achieved only with the help of eight transcription factors," said one of the authors of the study, associate professor at Kyushu University (Japan) Nobuhiko Hamazaki.
The discovery of stem cells and the ability to create them from "reprogrammed" adult tissues has given scientists hope that they can be turned into germ cells that can be implanted into the human body. This would solve the problem with infertility, which affects about one in ten inhabitants of the first World countries.
In recent years, molecular biologists have taken several big steps to solve this problem. In particular, seven years ago, Japanese researchers created the first "artificial" spermatozoa, and three years ago they turned reprogrammed mouse stem cells into eggs and raised offspring from them. Last year, scientists for the first time grew "blanks" of eggs that can be implanted into female animals or women.
Because of this, scientists wondered if it was possible to find a relatively small combination of genes, the activation of which would be guaranteed to turn stem cells into eggs or their preparations, like the so–called "Yamanaki factors" - four genes with which you can get stem cells from any body tissue.
Hamazaki and his colleagues made the first such discovery by observing how the activity of various genes changes as follicle cells turn into oocytes – germ cells with a double set of chromosomes that can form full-fledged eggs, in the nucleus of which there is only one copy of the genome.
Man-made life
First of all, biologists were interested in genes that are responsible for the assembly of so–called transcription factors - protein molecules that can connect to DNA and suppress or activate single genes or their chains. Scientists have suggested that the process of converting the "billets" of germ cells into oocytes is accompanied by the inclusion of several DNA sites that control the production of transcription factors – proteins that are responsible for this transformation.
Guided by this idea, biologists tracked how genes are turned on at different phases of oocyte development. Thanks to this, they identified 27 DNA sites and associated proteins that are presumably involved in this process. After that, Hamazaki and his colleagues tried to isolate the most important of them by accidentally disabling the genes that control the production of these transcription factors.
It turned out that only eight genes played such a role – FIGLA, SOHLH1, LHX8, NOBOX, STAT3, TBPL2, DYNLL1 and SUB1. Having identified these DNA sites, Japanese biologists tried to turn embryonic stem cells into oocytes by forcibly activating these transcription factors.
To their great surprise, in just five days such a simple technique turned a significant part of stem cells into egg preparations directly, bypassing all intermediate phases of their growth. Moreover, further experiments showed that something similar could be achieved using only four genes - NOBOX, FIGLA, TBPL2 and LHX8. However, the effectiveness of the procedure for their transformation has significantly decreased.
Having achieved such success, Hamazaki and his colleagues tested whether it was possible to turn man-made oocytes into eggs and fertilize them. Further experiments showed that this was indeed the case, despite the fact that the chromosomes of "artificial" oocytes were not organized exactly as they are arranged and arranged in their natural counterparts.
In the near future, Japanese biologists plan to solve this problem. If they succeed, then it will be possible to fully grow eggs and spermatozoa from reprogrammed stem cells. With this, it is possible to solve most of the problems associated with infertility and the inability of a significant part of married couples to conceive a child.
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