September 30, 2022

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Nature: Stem cells “transform” and fertilize “oocytes” by only 8 transcription factors

Nature: Stem cells “transform” and fertilize “oocytes” by only 8 transcription factors

Nature: Stem cells “transform” and fertilize “oocytes” by only 8 transcription factors. Break the laws of nature! Nature reveals: Only 8 transcription factors are needed, stem cells “transform” and fertilize “oocytes”.

The following article is from Biological Exploration

Break the laws of nature! Nature reveals that only 8 transcription factors are needed to “transform” stem cells into fertilized “oocytes”, making the impossible possible and breaking the “destiny”, which seems to be the goal that scientists have always been happy to pursue.

Nature: Stem cells "transform" and fertilize "oocytes" by only 8 transcription factors

More than 40 years ago, the birth of the world’s first test-tube baby broke the history of human beings’ natural gestation of life, and brought hope for infertility patients. Since then, the continued development of assisted reproductive technology has become an important means for more and more people to continue their offspring and improve their fertility civilization. However, this technology requires participants to provide healthy sperm and eggs. How to keep improving and bring better solutions for infertility patients has become the direction of scientists’ efforts.

On December 16, local time, “Nature” published a report entitled “Reconstitution of the oocyte transcriptional network with transcription factors”, which brought new hope for infertility patients to break the “curse” of infertility. .

Researchers at Kyushu University in Japan analyzed the development of mouse oocytes and uncovered the mysterious part of the gene network that regulates the growth of oocytes, and identified 8 transcription factors that are sufficient to trigger the growth of oocytes. These transcription factors can directly transform pluripotent stem cells into oocyte-like cells, and the transformed cells can be fertilized and divided like oocytes.

Nature: Stem cells "transform" and fertilize "oocytes" by only 8 transcription factors
Picture https://doi.org/10.1038/s41586-020-3027-9

Oocytes are unique germ cells in the female body. Its maturation is the first step in the process of gestating life. The cytoplasm of this special germ cell contains a variety of mixed substances, which can produce more than 200 highly differentiated cells necessary for human development.

In order to understand the factors that affect the growth of oocytes, the researchers established a culture system that used embryonic stem cells (ES) to reproduce the differentiation of female mouse germ cells, and mapped the female germ cells through RNA sequencing (RNA-seq) analysis. Developmental trajectory, found that there are 27 transcription factors that may be related to the oocyte development process.

Among them, only 8 transcription factors, Lhx8, Sohlh1, Nobox, Tbpl2, Stat3, DYNL1, Sub1 and Figla, are key factors and affect each other. Among them, Lhx8, Sohlh1, Nobox, and Tbpl2 form a core regulatory network, while Stat3, DYNL1, Sub1, and Figla are closely connected.

    
Picture 8 transcription factors are key factors affecting the growth of oocytes

Therefore, the researchers further analyzed whether these eight transcription factors can induce the transformation of mouse pluripotent stem cells into oocytes. The results are surprising. These transcription factors contribute to the production of oocytes. Researchers named these cells “directly induced oocyte-like cells” (DIOLs). Although these cells did not undergo meiosis, they were able to fertilize and divide to the 8th stage of embryonic development. Cell stage, after which development will be affected.

Nature: Stem cells "transform" and fertilize "oocytes" by only 8 transcription factors
Picture DIOLs can be fertilized and developed to the 8-cell stage

Professor Katsuhiko Hayashi of Kyushu University’s Faculty of Medicine said: “The cytoplasm from oocytes is a valuable resource in reproductive biology and medicine. Our research provides a novel method for obtaining a large number of egg cells without invading the human body. Oocyte-like cells without having to follow the same sequence of steps that occur naturally. Although it is too early for this technology to be applied to humans, experiments in mice have already shown us signs.”

In fact, since entering the 21st century, scientists have made a series of major breakthroughs in the field of assisted reproduction. As early as 2003, Hans R. Scholer published a groundbreaking research report in “Science”, proposing that mouse embryonic stem cells (ESC) can be induced to differentiate into egg-like cells in vitro, which caused a sensation in academia.

Nature: Stem cells "transform" and fertilize "oocytes" by only 8 transcription factors
Image DOI: 10.1126/science.1083452

In 2016, Chinese scientists realized the in vitro differentiation of mouse embryonic stem cells and obtained functional sperm (like) cells. At the same time, they used assisted reproduction methods to give birth to healthy mouse offspring, bringing hope to the offspring of azoospermic men. Related reports were published in the authoritative stem cell journal “Cell Stem Cell”.

Nature: Stem cells "transform" and fertilize "oocytes" by only 8 transcription factors
Picture https://doi.org/10.1016/j.stem.2016.01.017

With the continuous advancement of research and the continuous maturity of technologies such as “artificial eggs” and “artificial sperm”, people who are difficult to bear in the future will face more treatment options. Perhaps one day, it will also become a reality for men and women to conceive offspring by themselves.


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