Scientists successfully created male spermatogonial stem cells

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Cell Stem Cell: Scientists successfully created male spermatogonial stem cells

Scientists from Kyoto University and other institutions in Japan have discovered through research that the pluripotent stem cells of the mouse body can differentiate into functional sperm.

These sperm can be successfully used to produce healthy and fertile offspring. In addition, the research in this article also provides The most comprehensive model to date that can generate male germ cells in a test tube.

The development of male germ cells in mammals includes three different stages, namely the development of primordial germ cells (PGC) and the development of spermatogonia from male germ cells.

The standardization and subsequent spermatogenesis process. For species that rely on sexual reproduction (including mice and males), offspring may only be produced when sperm from males fertilize eggs from females; even artificial insemination techniques rely on donors for these two types of cells.

Recently, in a research report titled “In vitro reconstitution of the whole male germ-cell development from mouse pluripotent stem cells” published in the international journal Cell Stem Cell , scientists from Kyoto University and other institutions in Japan found through research that The pluripotent stem cells of the mouse body may be able to differentiate into functional sperm. These sperm can be successfully used to produce healthy and fertile offspring. In addition, this study also provides the most comprehensive method of producing male germ cells in test tubes to date. Model.

Scientists successfully created male spermatogonial stem cells

source: https://www.sciencedirect.com/science/article/abs/pii/S1934590921003428?via%3Dihub

Pluripotent stem cells allow scientists to study how every cell in the body is formed. Brain cells, heart cells and liver cells are just a few examples of the cell types produced by these stem cells. They are now being used as experimental cell therapies. Used in human patients, however, some cell types are difficult to prepare from pluripotent stem cells, especially sperm cells.

Among all cell types, germ cells are unique for many reasons. First, unlike other cells that carry 46 chromosomes, germ cells have only 23 chromosomes. All chromosomes of an egg come from the mother, while all chromosomes of a sperm come from the mother. From father.

In addition, it is the only cell that parents actually pass on to offspring, which may make it a driving force for maintaining and evolving species.

Although later researchers still need to do more research, but now they have made significant progress in how to use pluripotent stem cells to make sperm cells, at least for mice, the process is generally divided into three stages It can imitate the natural development process.

First, the stem cells will differentiate into primordial germ cells, and then they will differentiate into spermatogonial stem cells. This is when the male sex is determined, and finally differentiate into sperm. Spermatogonial stem cells can eventually produce sperm in men, but the facts show that the second stage is difficult to recreate in the laboratory; although the process is very difficult, it is not impossible to achieve.

Spermatogonial stem cells from mice can be produced. But the efficiency is very low, which is why researchers need to optimize the process. Researcher Dr. Yukiko Ishikura said that the rate of differentiation in mice is about a week slower, and the contribution of spermatogonial stem cells to sperm production is very low.

Starting from mouse pluripotent stem cells, the researchers prepared primordial germ cells and examined more than 10,000 primordial germ cells using the so-called new reconstituted testis method under 8 different conditions.

In order to verify the optimal conditions for the production of spermatogonial stem cells, the researchers confirmed that these cells have several common characteristics with cells in the mouse testis, including the expression of key genes, epigenetic characteristics, and transient upregulation of reverse transcripts. .

The control of retrotransposon can be recaptured. The researchers said that the regulation of retrotransposon is a special mechanism that can control the effect of retrotransposon on key genes through random repetitive regulation. The effect of expression.

Scientists successfully created male spermatogonial stem cells

Immunofluorescence analysis.

Image source: Takuya Sato, an assistant professor at Yokohama City University

The same epigenetics is also very important. Although genes are composed of DNA, their expression depends on epigenetic factors such as DNA methylation. Germ cells show a difference from DNA during their development.

The patterns of methylation, which are critical to an individual’s ability to produce offspring. In order to confirm that spermatogonial stem cells behave like spermatogonial cells produced in the body, the researchers injected laboratory-made spermatogonial stem cells into the mouse testis to allow the cells to develop into sperm cells. These sperm can be harvested and injected into the testis.

From the eggs, embryos are grown. However, these embryos can be used to conceive the mice so that healthy and fertile offspring can be born.

The results of this article provide the most comprehensive reconstitution process of male germ cell development from pluripotent stem cells so far; this research is also the first time that scientists have used mouse pluripotent stem cells to rebuild functional sperm in a test tube.

It provides new possibilities for the differentiation of male sperm cells. In summary, the results of this article show that by reproducing the three stages of male germ cell development, researchers may create a new paradigm for in vitro male gametogenesis of pluripotent stem cells .

(sourceinternet, reference only)

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