Another step towards in vitro eggs
Human stem cells turned into egg precursors
Daria Spasskaya, N+1
For the first time, Japanese scientists were able to turn induced human pluripotent cells into precursors of female germ cells – oogonia. This was done in vitro in an artificial mouse ovary. The work was published in Science (Yamashiro et al., Generation of human oogonia from induced pluripotent stem cells in vitro).
The targeted production of germ cells from stem cells has long been an unsolvable task for scientists, nevertheless, in recent years there has been a significant breakthrough in this area. Thus, scientists managed to obtain functional spermatogonia and oocytes (male and female germ cells) of mice from pluripotent stem cells by transplantation into the testicles or by incubation with ovarian tissues. However, human cells have so far been reprogrammed only into primordial germ cells – the earliest stage of development of future germ cells, which are released by the second week of fetal development. The cells did not want to develop beyond this stage.
Now scientists led by Mitinori Saitou from Kyoto University have managed to overcome this barrier and take a step forward – to turn the obtained primordial human cells into oogonies. The latter are the precursors of oocytes (eggs) – these cells still have a double set of chromosomes, and actively divide with the help of mitosis. The further development of oogonia involves division by meiosis with the formation of haploid (that is, with one set of chromosomes) oocytes.
In the experiment, scientists reprogrammed human pluripotent stem cells into primordial germ cells, and then placed them in a reconstructed in vitro mouse ovary to create the right microenvironment and provide access to a complex cocktail of developmental factors. Some of the cells survived in the artificial ovary (they were monitored using a fluorescent reporter gene embedded in the genome), and on the 77th day of incubation, scientists found that the cells began to express markers characteristic of the next stage of development – female oogonia and male gonocytes. In addition, epigenetic rearrangements characteristic of oogonia and gonocytes were observed in the cells, in particular, DNA demethylation.
Scheme of an experiment on joint incubation of stem cells differentiated into germ germ cells (hPGCLC) in a mouse ovary reconstructed from embryonic cells. A drawing from an article in Science.
Despite the fact that human progenitors of germ cells began to express marker genes for entry into meiosis, they did not begin dividing even after four months of incubation. Mouse cells, meanwhile, after three weeks of incubation in the "ovary" moved to the next stage and formed oocytes. Despite the fact that the authors of the work have not yet been able to figure out why the environment of the mouse ovary suppresses meiosis in human cells, they are working on this problem. Previously, Chinese scientists were able to start meiosis in vitro in mouse sperm precursors by forming an artificial testicle from the cells of a newborn mouse. Mitinori Saitu's scientific group was also engaged in obtaining spermatozoa in vitro, however, they managed to do this only by transferring the precursors to the mouse testicles.
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