Science

Scientists in various fields have tried for years to figure out how paternal-only DNA could sustain a mammal through all stages of life.

A small team of researchers has reported a striking achievement: they succeeded in raising a mouse that came from two male parents, and it grew into a healthy adult. Their work unveils a set of genetic changes that overcomes the imprinting barriers that typically block such development.

Scientists in various fields have tried for years to figure out how paternal-only DNA could sustain a mammal through all stages of life.

Biological imprinting is an inherited pattern of gene expression. It involves certain genes getting turned on or off depending on whether they come from the father or the mother.

Researchers found that if you adjust a selection of these imprinting genes, you can open the door for unique reproductive feats, such as an embryo that starts with only paternal cells.

“This work will help to address a number of limitations in stem cell and regenerative medicine research,” explains Wei Li of the Chinese Academy of Sciences in Beijing.

In this case, the scientists homed in on key sections of DNA that are known to control fetal growth and viability.

What this means for biology

When a mouse embryo is formed in the usual way, paternal and maternal DNA come together. That combination produces a precise balance of imprinted genes.

In paternal-only embryos, certain growth-related genes can become overstimulated, but the team was able to selectively modify them so these embryos could mature.

“These findings provide strong evidence that imprinting abnormalities are the main barrier to mammalian unisexual reproduction,” said Qi Zhou, co-lead of this study.

By re-engineering the problematic gene regions, the researchers made it possible for two sets of male chromosomes to support a developing mouse. Therapeutic ideas

A number of genetic and metabolic disorders in humans stem from errors in imprinting. Scientists have asked whether strategies used here might be adapted to correct imprinting problems that cause diseases in people.

One potential target is KCNK9, which has been linked to Birk-Barel syndrome. Precise gene editing of such imprinting sites could help in the design of improved treatments for these rare disorders.

In practice, these ideas may take time to progress. Mouse models are often a first step in studying how imprinting influences development.

The more scientists understand about restoring the right imprinting patterns, the closer they might come to tackling certain medical conditions. Gene imprinting implications

The modified imprinting genes not only allowed bi-paternal mice to survive to adulthood, they also improved the efficiency of stem cells used in the process.

The researchers reported that these engineered embryonic stem cells were about twice as likely to develop into full-term pups compared to unmodified cells.

This improved developmental stability could change how scientists approach cloning. Currently, cloned animals often suffer from low survival rates and severe abnormalities, in part due to faulty imprinting.

Fixing imprinting errors ahead of time might make future cloning methods more reliable, especially in complex mammals like primates. Ethical considerations

Questions often arise about how these approaches could extend to humans.

According to guidelines from the International Society for Stem Cell Research (ISSCR), heritable genome editing is not currently allowed for human reproductive purposes because it is considered unsafe.

Researchers continue to examine these practices in animal models before even considering steps that approach human application. Investigators involved in this work remain cautious.

While a mouse with two fathers has captured headlines, translating similar methods to people is a bigger leap.

The focus remains on unraveling how imprinted genes function, and how targeted interventions might fix imprinting-related diseases down the road. Next questions

There is still room to explore how best to refine these genetic strategies to improve survival rates and lessen the chance of complications.

Specialists are also looking at future animal models to see if placental differences, organ development, or immune responses undergo subtle changes when imprinting is modified.

Some foresee that data gleaned from these methods will shape the next generation of gene-editing research.

Ongoing studies point to a need for caution. Issues like longevity, fertility, and normal physiology require much deeper evaluation.

Still, scientists see value in applying these insights to refine cloning and enhance studies of embryonic stem cells. Even partial solutions could inform safer protocols for regenerating cells and tissues in healthcare settings.

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This breakthrough was led by Wei Li of the Chinese Academy of Sciences in Beijing and Qi Zhou of the same institution, with further input from collaborators at Sun Yat-sen University.

The study is published in Cell Stem Cell.