A study published online December 24 in "Cells" shows that scientists not only induce skin cells completely into inducible stem cells (iPS) in vitro, but also differentiate them into human primordial germ cells (hPGCLC, sperm and egg cells). ), the key gene of hPGCLC, the SOX17 gene and the marker substance, CD38 glycoprotein, were also found in vitro.

Release date: 2014-12-29

Israeli and British scientists cultivate human eggs and sperm, and the material comes from a human skin cell. The success of this research will take a step forward in the treatment of infertility, and of course there will be huge controversy and safety review. The study, published online December 24 in "The Cell," scientists first induced skin cells into induced stem cells (iPS), which can differentiate into any cell, including sperm and eggs.

Since October 2012, Kyoto University molecular biologist Katsuhiko Hayashi and stem cell scientist Mitinori Saitou have received many elder mails in vitro, and most of these couples are middle-aged. Still anxious for one thing: want a child. One of the British women who had been menopaused was willing to come to his laboratory in Kyoto University for help. She wrote: "This is my only wish."

Looking back at the 2012 paper, the researchers thought that only developmental biologists would be interested in his experimental results. Under in vitro conditions, mouse skin cells are used to create primordial germ cells (PGCs) that can develop into sperm and eggs. To prove that the primordial germ cells cultured in these laboratories are similar to the naturally-developed primordial germ cells, the researchers used them to generate eggs, which in turn created mouse life.

Professor Hayashi said at the time that the life of the created mouse was only a "by-product" of his research, and his research would mean more - using the skin cells of infertile women to provide them with fertile eggs. At the same time, he also suggested that male skin cells can also be used to create eggs. Similarly, female skin cells can also produce sperm. (In fact, after the results of the study were published, many gays sent emails to Hayashi for more information.)

This kind of cell originates from the process of embryonic development, and the individual can produce sperm cells and egg cells after adulthood.

Past human cell culture in vitro attempts: very low success rate

Stem cytologist Professor Saitou uses animal skin cells to induce stem cells, and embryonic stem cells can do the same. Although his cells could not continue to develop, Saito found that if these cells were transplanted into the mouse testis, the cells could differentiate and mature and produce functional sperm. If the cells were transplanted into the mouse ovary, the cells would It can differentiate into mature and produce functional eggs, which can be fertilized in the body. The same attempts at human cells have also been partially successful, and germ cells can be cultured in vitro, but the success rate is very low and more research is difficult.

First complete in vitro culture of mature sperm and egg cells

The study, conducted by the Azim Surani team at the University of Cambridge in the United Kingdom and the Jacob Hanna team at the Weizmann Institute of Science in Israel, pioneered the complete in vitro culture of mature sperm and egg cells.

The key to the success of biologists is to find the right starting point. A major obstacle to the culture of human cells in vitro is that mice and human embryonic stem cells are fundamentally different. Mouse embryonic stem cells are "naive" - ​​easily induced to differentiate into any path; while human stem cells are "mature" and their differentiation The way can't adapt to all the ways. Hanna and his team then established a way to down-regulate the differential genetic signaling pathway, thereby constructing a new type of iPS cells, which they named "na?ve cells." These primitive cells appear to make iPS cells more rejuvenated, closer to the original embryonic state that can truly differentiate into all cell types. Since these primordial cells are more similar to their mouse counterparts, Hanna and the team believe they can be induced to differentiate into primordial germ cells.

Professor Hanna and his collaborators recognized this in a paper last year, and they wrote in the paper that the above difficulties can be overcome by transforming cells.

As stated in their published paper, Primordial germ cells (PGCs) can differentiate into spermatogonia and differentiate into ovipotent cells before they enter the genital warts. Determined by the combination of different genital ridge cells. This time, their research constructed an easy-to-manage experimental model, using embryonic stem cells into human primordial germ cells (PGCs), hPGCL-like cells, and found that SOX17 is the key to cultured mature sperm and egg cells in vitro. The gene, CD38 glycoprotein, is a marker added to the surface of human primordial germ cells (hPGCLC).

By adding a red-emitting fluorescent marker (CD38 glycoprotein) to a portion of the primordial germ cell, the researchers can accurately estimate the number of reprogrammed primordial germ cells, and the results show very high efficiency – up to 40 % of the cells become primordial germ cells; this amount enables simple analysis.

The scientists also said that primordial germ cells are only the first step in building human sperm and eggs. In the laboratory, a series of events can be completed, and the adult cells face many obstacles before they pass through the embryonic stem cell cycle and become sperm or eggs. For example, at some point in the process, these cells must learn a stunt: divide their DNA into two halves before they become viable germ cells.

From the pictures provided by the researchers' published articles, it can be seen that the human gene network is completely different from the gene network previously identified in mice, which may have a significant impact on the future research of primordial germ cells and other early embryonic cells.

Source: biodiscover

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