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The many types of cells in the human body are produced through the process of differentiation, in which stem cells develop into more specialized types. Currently, it is a challenge for researchers to control the differentiation of stem cells in the laboratory (in vitro). Of particular interest are oocytes, which are female germ cells that develop into eggs. Understanding its development could have far-reaching impacts, from treating infertility to conserving endangered species. A new study by a Japanese team of researchers led by Dr. Mitinori Saitou has successfully induced meiotic (dividing) oocytes from cynomolgus monkey embryonic stem cells, which share many physiological traits with humans. By establishing a culture method to induce meiotic oocyte differentiation, the researchers attempted to shed light on germ cell development in both humans and other primates. The study findings were published in the March 2023 issue of The EMBO Journal.
The team previously reported conditions for inducing oogony, the precursors of oocytes, by aggregating human primordial germ cell-like cells (hPGCLC) with cells from the ovaries of female mouse embryos and then culturing them under air-liquid interface conditions.1. Similarly, PGCLCs from cynomolgus monkeys were induced to differentiate into oogonia but did not progress to meiotic oocytes. To overcome this obstacle, the induced oogonia were isolated and re-aggregated with somatic cells from the ovaries of female mouse embryos and re-cultured.
Under these new culture conditions, the differentiation into meiotic oocytes of cynomolgus monkey oogonia was successfully induced, but their development was arrested in the second stage of meiosis. Single cell transcriptome analysis showed that oocyte transcriptomic dynamics in vitro (in the laboratory) were similar to those of oocytes live (in our body). The researchers also identified differences in gene expression between the in vitro and live oocytes, which suggested a bottleneck for in vitro oocyte development that could lead to meiosis arrest in vitro.
Furthermore, by performing a genome-wide methylome analysis, the authors found that induced oocytes were involved in the process of genome-wide demethylation. in vitro, as seen in developing mouse and human female germ cells. They also noted that demethylation behaved differently on paternally and maternally derived X chromosomes. These unique methylation dynamics were also found in induced human oogonia. in vitro, suggesting that the mechanisms underlying female germ cell development may be the same in all primate species. Therefore, this culture system could be useful as a model of the primate germ cell differentiation process.
When asked about the potential impact of their study, the authors said their multi-step reconstitution method in female germ cell development may help to clarify the molecular mechanisms of primate oocyte development and could one day contribute. to the treatment of deficient development of oocytes in reproductive medicine. First author, Dr. Sayuri Gyobu-Motani, says: “We hope that our farming system can help in the conservation of endangered species and the creation of in vitro oocyte induction systems for other long-lived mammalian species”.
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