Scientists have created mice with cells from two males by converting the XY chromosome set to XX without an additional Y chromosome in mouse pluripotent stem (PS) cells

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In a groundbreaking experiment, scientists successfully created baby mice using genetic material from two male mice.

The research has raised hopes that the technique could eventually be used to help same-sex human couples have biological children.

This raises the distant possibility of using the same technique for people – although experts caution that very few mouse embryos developed into live mouse pups and no one knows whether it would work for humans.

Still, “It’s a very clever strategy,” said Diana Laird, a stem cell and reproductive expert at the University of California, San Francisco, who was not involved in the research.

“It’s an important step in both stem cell and reproductive biology.”

Scientists described their work in a study published Wednesday in the journal Nature.

The technique used in the study is highly complex and involves several stages. First, the scientists took skin cells from the tails of male mice and transformed them into “induced pluripotent stem cells”. These cells can then be transformed into any type of cell in the body.

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Confocal microscopic image of a colony of human induced pluripotent stem cells derived from a patient with oculocutaneous albinism. Red indicates transcription factor Oct-4, green the protein SSEA4, and blue the nuclei of the cells.
NIH Image Gallery from Bethesda, Maryland, USA – Human induced pluripotent stem cell colony
Researchers at NIH’s National Eye Institute (NEI) developed the first patient-derived stem cell model for studying eye conditions related to oculocutaneous albinism (OCA). Learn more: at https://www.nih.gov/news-events/news-releases/nih-researchers-develop-first-stem-cell-model-albinism-study-related-eye-conditions In this image: A human induced pluripotent stem cell colony from OCA1A patient. The image was acquired using a confocal microscope and is stained for pluripotency marker proteins. The red color depicts transcription factor OCT4, green is SSEA4 protein and blue represents the nucleus of the cells. Credit: National Eye Institute/NIH

Induced pluripotent stem cells (iPSCs) are a type of stem cell that can be generated from somatic cells (such as skin cells) through a process called reprogramming. iPSCs are similar to embryonic stem cells (ESCs) in that they have the ability to differentiate into any cell type in the body, making them a valuable tool for research and regenerative medicine.

The process of generating iPSCs typically involves introducing specific transcription factors (proteins that regulate gene expression) into somatic cells. These transcription factors can reprogram the gene expression patterns of the somatic cells, causing them to revert to a pluripotent state similar to that of ESCs.

Once iPSCs have been generated, they can be maintained and expanded in culture, and can differentiate into a variety of cell types, including neurons, heart cells, and blood cells. This makes them a valuable tool for studying disease mechanisms, drug discovery, and cell-based therapies.

However, it is important to note that there are still many challenges associated with the use of iPSCs, including the potential for genetic and epigenetic abnormalities, variability in differentiation potential, and the risk of teratoma formation (a type of tumor that can arise from pluripotent stem cells). As such, continued research is necessary to fully understand the potential of iPSCs and to develop safe and effective therapies based on their use.

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Next, the researchers grew the stem cells in the lab and treated them with a drug that converted the male mouse stem cells into female cells. These female cells were then used to create functional egg cells, which were fertilized and implanted into female mice. Only 1% of the embryos – just 7 out of 630 – survived and grew into live mouse pups.

The pups appeared to grow normally and were able to become parents themselves in the usual way, research leader Katsuhiko Hayashi of Kyushu University and Osaka University in Japan told fellow scientists at the Third International Summit on Human Genome Editing last week.

In a commentary published alongside the Nature study, Laird and her colleague, Jonathan Bayerl, said the work “opens up new avenues in reproductive biology and fertility research” for animals and people. Down the road, for example, it might be possible to reproduce endangered mammals from a single male.

“And it might even provide a template for enabling more people,” such as male same-sex couples, “to have biological children, while circumventing the ethical and legal issues of donor eggs,” they wrote.

Another important issue is the possibility of mutations and errors being introduced during the process of creating eggs in the lab. This is a concern because genetic mutations can cause serious health problems, and it is not yet clear whether this new technique could introduce any genetic errors or abnormalities into the resulting offspring.

Additionally, while the researchers are excited about the possibility of using the technique to help same-sex couples have biological children, it is still a long way from being applicable to humans.

In normal mammalian development, males have one X and one Y chromosome (XY), while females have two X chromosomes (XX). The presence of the Y chromosome determines male sexual development, and its absence leads to female development. However, XX male complementation allows for male development to occur in an XX embryo by introducing a female factor that can compensate for the lack of a Y chromosome.

XX male complementation is a genetic technique that involves modifying male cells to express a female factor, which can compensate for the lack of a second X chromosome in the male genome. This allows the cells to develop into an XX embryo, which is typically associated with female development.

In this technique, male cells are genetically engineered to express a specific gene or genes that are normally only found on the X chromosome. These genes can be introduced through a variety of methods, such as using viral vectors or gene editing tools like CRISPR/Cas9. Once the male cells have been modified, they are used to fertilize an egg cell from a female mouse.

The resulting embryo will have two X chromosomes, one from the female egg and one from the modified male cells. This can lead to the development of a male mouse with XX chromosomes, which is typically associated with female development.

This technique has been used in a variety of research studies to investigate the role of genes in development and disease. However, it is important to note that such experiments are typically conducted for research purposes and are subject to strict ethical guidelines and regulatory oversight.

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