(Press-News.org) A team of stem cell scientists have successfully used embryonic stem cell engineering to create a bi-paternal mouse—a mouse with two male parents—that lived until adulthood. Their results, publishing on January 28, 2025, in the Cell Press journal Cell Stem Cell, describe how targeting a particular set of genes involved in reproduction allowed the researchers to overcome previously insurmountable challenges in unisexual reproduction in mammals.
Scientists have attempted to create bi-paternal mice before, but the embryos developed only to a certain point and then stopped growing. Here, the investigators, led by corresponding author Wei Li of the Chinese Academy of Sciences (CAS) in Beijing, focused on targeting imprinting genes, which regulate gene expression in a number of ways. “This work will help to address a number of limitations in stem cell and regenerative medicine research,” says Li.
“The unique characteristics of imprinting genes have led scientists to believe that they are a fundamental barrier to unisexual reproduction in mammals,” says co-corresponding author Qi Zhou, also of CAS. “Even when constructing bi-maternal or bi-paternal embryos artificially, they fail to develop properly, and they stall at some point during development due to these genes.”
Earlier attempts to make a bi-paternal mouse used ovarian organoids to derive oocytes from male pluripotent stem cells; those ooctyes were then fertilized with sperm from another male. However, when the homologous chromosomes—the chromosomes that divide during meiosis to create oocytes and sperm—originated from the same sex, imprinting abnormalities arose, leading to severe developmental defects.
In this study, the researchers modified 20 key imprinting genes individually using a number of different techniques, including frameshift mutations, gene deletions, and regulatory region edits. They found that not only did these edits allow the creation of bi-paternal animals that sometimes lived to adulthood, but they also led to stem cells with more stable pluripotency.
“These findings provide strong evidence that imprinting abnormalities are the main barrier to mammalian unisexual reproduction,” says co-corresponding author Guan-Zheng Luo of Sun Yat-sen University in Guangzhou. “This approach can significantly improve the developmental outcomes of embryonic stem cells and cloned animals, paving a promising path for the advancement of regenerative medicine.”
The researchers note several limitations that their work still needs to address. For one thing, only 11.8% of the viable embryos were capable of developing until birth, and not all the pups that were born lived to adulthood due to developmental defects. Most of those that did live to adulthood had altered growth and a shortened lifespan. Also, the mice that lived to adulthood were sterile, although they did exhibit increased cloning efficiency.
“Further modifications to the imprinting genes could potentially facilitate the generation of healthy bi-paternal mice capable of producing viable gametes and lead to new therapeutic strategies for imprinting-related diseases,” says co-corresponding author Zhi-Kun Li of CAS.
The team will continue to study how modifying imprinting genes may lead to embryos with higher developmental potential. They also aim to extend the experimental approaches developed in mice to larger animals, including monkeys. However, they note that this will require considerable time and effort because the imprinting gene combinations in monkeys differ significantly from those in mice. Whether this technology will ultimately be applied towards solving human disease remains unclear. The International Society for Stem Cell Research's ethical guidelines for stem cell research does not allow heritable genome editing for reproductive purposes nor the use of human stem cell-derived gametes for reproduction because they are deemed as currently unsafe.
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Cell Stem Cell, Li et al. “Adult bi-paternal offspring generated through direct modification of imprinted genes in mammals.” https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(25)00005-0
Cell Stem Cell (@CellStemCell), published by Cell Press, is a monthly journal that publishes research reports describing novel results of unusual significance in all areas of stem cell research. Each issue also contains a wide variety of review and analysis articles covering topics relevant to stem cell research ranging from basic biological advances to ethical, policy, and funding issues. Visit: http://www.cell.com/cell-stem-cell. To receive Cell Press media alerts, contact press@cell.com.
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WASHINGTON, Jan. 28, 2025 – Cancer accounted for nearly 10 million deaths in 2020 – almost one in every six deaths globally – according to the World Health Organization. Because the detection of abnormal diseased cellular growth often occurs too late, timely cancer diagnosis remains one of humanity’s most pressing and elusive medical objectives. Recent research has focused on the detection in peripheral blood of rare circulating tumor cells (CTCs), which serve as noninvasive markers that can help inform diagnoses.
It is inherently difficult to separate controllable target cells to examine. Traditional ...
A new study published today in JAMA Network Open explores the effects of both recent and lifetime cannabis use on brain function during cognitive tasks.
The study, the largest of its kind ever to be completed, examined the effects of cannabis use on over 1,000 young adults aged 22 to 36 using brain imaging technology. The researchers found that 63% of heavy lifetime cannabis users exhibited reduced brain activity during a working memory task, while 68% of recent users also demonstrated a similar impact.
This decline in brain activity was associated with worse performance on working memory - the ability to retain and use information to perform tasks. For example, working ...
About The Study: Lifetime history of heavy cannabis use was associated with lower brain activation during a working memory task in this study of young adults. These findings identify negative outcomes associated with heavy lifetime cannabis use and working memory in healthy young adults that may be long lasting.
Corresponding Author: To contact the corresponding author, Joshua L. Gowin, PhD, email joshua.gowin@cuanschutz.edu.
To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/
(doi:10.1001/jamanetworkopen.2024.57069)
Editor’s Note: Please see the article for additional information, including ...
Researchers from the University of Pittsburgh have developed a new way to grow T cells in the lab that enables them to live longer and better destroy cancer cells in a mouse model of melanoma compared to those grown in traditional growth media.
The findings, published recently in Cell Metabolism, have the potential to greatly improve the effectiveness of cancer immunotherapies that involve taking T cells from a patient and growing them to enormous numbers in the lab before reinfusing them back into the body.
“The way we traditionally grow T cells ...
About The Study: In this cohort study, exposure to cold in the Netherlands and heat in Spain were associated with more psychiatric symptoms, highlighting distinct temperature exposure and mental health associations among adolescents. Future studies should explore this across diverse climates to further quantify the intricate and multifactorial association of climate change with mental health.
Corresponding Author: To contact the corresponding author, Monica Guxens, MD, email monica.guxens@isglobal.org.
To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/
(doi:10.1001/jamanetworkopen.2024.56898)
Editor’s ...
About The Study: In pregnant patients with uncomplicated chronic hypertension, prevention of preeclampsia may potentially reduce severe maternal morbidity risk comparable to normotensive patients.
Corresponding Author: To contact the corresponding author, Erica P. Gunderson, PhD, MPH, email erica.gunderson@kp.org.
To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/
(doi:10.1001/jamanetworkopen.2024.51406)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding ...
PHILADELPHIA—Standardizing an assessment process currently used by doctors during care discussions with veterans at risk for suicide in other context could shed more light on the risks related to firearms and opioids.
The findings from researchers at the Perelman School of Medicine at the University of Pennsylvania were reported today in JAMA Network Open. They found that fewer veterans reported having access to firearms than expected—either because some didn't mention it to their doctor, it wasn't ...
Fukuoka, Japan—It goes without saying that the tourism industry in Japan is booming. Walk around any major city and you’ll see people from all around the world enjoying the country’s food, culture, and hospitality. Naturally, the revenue generated by the industry has had a positive economic impact throughout Japan. However, between 2020 and 2022, the tourism industry was hit particularly hard due to the COVID-19 pandemic and subsequent travel restrictions. While the government implemented policies ...
A new study has taken a closer look at how healthcare quality is measured in three major countries—Israel, the United States, and the United Kingdom—uncovering striking similarities and critical gaps. The research delved into Israel’s Quality Indicators in Community Healthcare (QICH), the US’s Healthcare Effectiveness Data and Information Set (HEDIS), and the UK’s Quality and Outcomes Framework (QOF). While all three systems prioritize family medicine and process-focused metrics, the study highlights a lack of attention to structural and outcome-based ...
Antarctica, often regarded as the planet’s last true wilderness, harbours unique ecosystems that support extraordinary biodiversity and contribute to global diversity and environmental stability. These ecosystems, which occupy permanently ice-free land covering less than 0.5% of the continent, are now under growing threat from human activity and climate change.
Now, a team led by researchers at UNSW Sydney’s Centre for Ecosystem Science has developed a high-resolution map and hierarchical classification system of Antarctica’s ice-free lands, which can be seen in full in Scientific Data.
This new inventory categorizes Antarctica’s ecosystems ...
