Publication highlights

Human induced pluripotent stem cells (iPSCs) mimic early embryos and can become any cell type, making them a powerful tool to study development and disease. However, most existing cell lines aren't suited to study sex differences. In collaboration with AstraZeneca, Turner lab researchers Ruta Meleckyte and Wazeer Varsally addressed this by creating new iPSCs with either XX (female) or XY (male) sex chromosomes. All other chromosomes were identical, so any differences observed can be linked to sex. These openly available iPSCs will enable more accurate modelling of sex-specific biology and may help in developing better, more personalised treatments in the future.

Researchers at the Francis Crick Institute have revealed insight into why embryos erase a key epigenetic mark during early development, suggesting this may have evolved to help form a placenta. The team at the Crick investigated, for the first time, epigenetic changes in embryos of a marsupial, which diverged from eutherian mammals 160 million years ago. They created a map of DNA methylation in opossum eggs, sperm and embryos, finding that levels of methylation in eggs and sperm were more similar to each other than they were in eutherians. However, unlike eutherians, opossum embryos did not undergo a full wiping event. Instead, DNA methylation was retained in the early embryo, with loss occurring much later, and DNA demethylation was largely restricted to a specific supportive tissue called the trophectoderm, which becomes the marsupial placenta. These findings show that demethylation isn’t universally required for formation of an early mammalian embryo, instead, based on their findings, the team believe that wiping may have evolved specifically for the development of the placenta.

Researchers at the Crick have uncovered which genes on the Y chromosome regulate the development of sperm and impact fertility in male mice. They generated thirteen different mouse models, each with different Y genes removed, and investigated their fertility. The team found that several Y genes were critical for reproduction, and that if these genes were removed, the mice couldn’t produce young. Some other genes had no impact when removed individually, but did lead to the production of abnormal sperm when removed together. The results suggest that many Y genes play a role in fertility and can compensate for each other if one gene is lost. This also means that some cases of infertility likely result from multiple genes being deleted at the same time.

Researchers at the Crick have now developed a way to grow specialised left ventricular heart muscle cells from stem cells, opening up new opportunities for research into heart disease, drug screening, and potentially the development of new treatments.

Their methods are published today in Cell Reports Methods and have also been licensed to Axol Bioscience to commercialise the protocol for the generation and sale of cardiomyocytes for R&D and the provision of contract research services, especially in field of drug screening and cardiotoxicity assays.

Researchers in the Turner lab, in collaboration with the University of Kent, used gene editing technology to create female-only and male-only mice litters with 100% efficiency. Targeting the Top1 gene, which is essential to DNA replication and repair, their method uses CRISPR-Cas9 to induce sex-linked lethality before embryo implantation, allowing only the desired sex to develop. This proof of principle study demonstrates how the technology could be used to improve animal welfare in scientific research and perhaps also agriculture.