Base Editing in Human Embryos Reveals Critical Gene for Development
Altering a single gene in human embryonic cells has enabled insights into early human development.
Precision gene editing has been used for the first time to study human embryogenesis.
By altering a single nucleotide base pair, researchers have uncovered a key role of the NANOG gene in embryo development.
Understanding how embryos develop
The genes and pathways behind the formation of the first human cell lineages during embryogenesis could have clinical implications for regenerative medicine, pregnancy loss, and infertility.
Steps in early embryogenesis:
1. Egg and sperm fuse, forming a single-cell zygote.
2. The zygote rapidly produces new cells via mitotic cell division.
3. Diving cells begin to differentiate.
4. A blastocyst forms; trophoblastic cells, which help the embryo implant, surround a fluid-filled cavity and the inner cell mass.
5. Cells in the inner cell mass differentiate into the epiblast, which forms fetal germ cells, and the hypoblast, which goes on to form the yolk sac.
6. The embryo undergoes implantation into the uterus.
However, studying these processes in human embryos has been challenged by ethical, technical, and biological constraints. While mouse models have been informative for identifying transcription factors, human development doesn’t always follow the same trajectory.
Studying how transcription factors function in human embryos has been limited by genome-editing approaches that induce genotoxicity, leading Professor Kathy Niakan and her colleagues to utilize base editing in their new study.
Base editing
Base editing changes a single nucleotide base pair without making double-strand DNA breaks, acting like a more precise version of CRISPR/Cas9 genome editing.
“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,” said Niakan, a group leader at the University of Cambridge Loke Center for Trophoblast Research.
A focus on NANOG
NANOG is key for mouse embryogenesis, with studies showing that its loss disrupts the epiblast—the layer of pluripotent primary cells that give rise to germ cells and embryonic stem cells—and the yolk sac, which supports the developing embryo. It is also a key regulator of human embryonic stem cell identity, helping to maintain the balance of self-renewal and differentiation.
“We had predicted that the gene called NANOG would have a really important role in human development, given its importance in the development of mouse embryos,” said Dr. Katarina Harasimov, who contributed to the study.
In early human embryos, NANOG expression is restricted to the epiblast, but the mechanisms underlying NANOG’s role in epiblast pluripotency and specification remain unclear.
Improving Oral Bioavailability Prediction With Human Models
Join this webinar to explore how an integrated human gut/liver microphysiological system (MPS), combined with mechanistic modeling, provides deeper insight into oral drug disposition.View Webinar
Using base editing, Niakan and her team precisely targeted the NANOG gene to functionally knock out its expression in very early-stage human embryos.
Without NANOG expression, cells of the early embryo couldn’t develop into the epiblast. However, the cells that go on to establish tissues that support the developing embryo could still form.
“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,” Niakan said.
The study also highlighted the importance of studying human development directly.
“What we found was that NANOG functions somewhat differently in humans than in mice, which means our assumptions about the role of this gene don’t transfer neatly across species,” explained Harasimov.
Base editing as a new way to study development
This work is the first to use base editing to study gene function in human embryos.
Scaling Genome Editing From Discovery to Manufacturing
In this webinar, our expert speaker will discuss how non-viral electroporation-based genome editing supports applications ranging from CRISPR screening to complex cell engineering.View Webinar
As part of the research, the authors assessed edit accuracy, chromosome loss, aneuploidy, and off-target RNA edits. They found that base editing made effective edits, had no genotoxicity, and low off-target effects, illustrating its potential for studying other developmental regulators.
“The precision of base editing is a major step from the previous generation of genome editing techniques. This allows us to study early human development with greater confidence,” said Dr. Oliver Bower, first author of the study.
Pluripotent cells, such as human embryonic stem cells, are widely used in biomedical research because of their ability to differentiate into any other cell type. Understanding how pluripotent cells arise in the developing embryo could also improve the use of these cells in research.
Bower added: “By pinpointing how genes like NANOG control the development of pluripotent cells, we can make stem-cell systems for biomedical research more predictable and reliable.”
Reference: Bower OJ, Orsi AER, McMahon R, et al. Base editing reveals an essential role for NANOG in human embryogenesis. Nature. 2026. doi: 10.1038/s41586-026-10792-1
This article is a rework of a press release issued by The University of Cambridge. Material has been edited for length and content.
Add Technology Networks as a preferred Google source to see more of our trusted coverage.
