Researchers at the University of Cambridge Loke Centre for Trophoblast Research announced on June 25 that a genome editing technique called base editing has been used to alter a single gene in human embryonic cells, providing new insights into very early human development. The team reported that base editing is a more precise version of the CRISPR/Cas9 genome editing method, capable of changing a single nucleotide base pair within the approximately 3 billion base pairs of the human genome.
By using this technique to block the NANOG gene in very early-stage human embryos, researchers found that these cells could not develop into specialized pluripotent cells known as the epiblast, which later form the body. However, other tissues such as those forming the placenta and yolk sac were still able to develop without NANOG.
The study marks the first time base editing has been applied to investigate gene function in human embryos. Researchers noted that this method's precision reduces unintended chromosomal abnormalities often associated with conventional CRISPR/Cas9 techniques. Professor Kathy Niakan at the University of Cambridge Loke Centre for Trophoblast Research said, "Base editing represents a significant advance on conventional CRISPR/Cas9 because it carries a far lower risk of causing unintended chromosome errors. Base editing can precisely change a single nucleotide base pair to another in an entire human genome of around 3 billion base pairs - that's an incredible feat." She added, "Our results indicate that the NANOG gene is critical for the development of pluripotent cells, the building blocks that are fundamentally important to human development."
Pluripotent cells have broad applications in biomedical research due to their ability to become any cell type in the body. Human embryonic stem cells originate from regions with high NANOG activation levels, leading scientists to suspect its importance. Dr. Katarina Harasimov from Cambridge's Loke Centre said, "We had predicted that the gene called NANOG would have a really important role in human development, given its importance in mouse embryos... What we found was that NANOG functions somewhat differently in humans to mice, which means our assumptions about this gene don't transfer neatly across species." Previous studies using mice showed loss of NANOG affected both epiblast and yolk sac tissues; however, this research indicates differences between species.
The embryos used were donated by couples who had completed IVF treatment and allowed surplus samples for research purposes under strict regulatory oversight from authorities including Britain's Human Fertilisation and Embryology Authority and Newcastle and North Tyneside Research Ethics Committee. The findings appear today in Nature journal following collaboration among several international institutions.
