Embryonic stem cell discovery creates opportunity to study our genomic ‘wake up call’

8 March 2022

Images showing human 8C-like cells among naïve embryonic stem cells (left) and 8-cell human embryos (right) fluorescently labelled for TPRX1 (green), H3.Y (red) and DNA (blue). The image shows the ZGA marker proteins TPRX1 and H3.Y are present in both cell populations. (Credit: Dr. Jasmin Taubenschmid-Stowers Babraham Institute, Dr. Fátima Santos Babraham Institute, Dr. Jennifer Nichols, Cambridge University)

Researchers from the Babraham Institute have published their latest work in the journal Cell Stem Cell describing a new subset of human embryonic stem cells that closely resemble the cells present at the genomic ‘wake up call’ of the 8-cell embryo stage in humans.

ScienceDaily explains that “this new stem cell model will allow researchers to map out the key genomic changes during early development, and help move towards a better understanding of the implications of genome activation errors in developmental disorders and embryo loss”.

“Our focus is now to characterise these cells and understand their unique properties so that we can use 8-cell like cells as a tool to ask questions about the molecular changes that may cause developmental issues at this early stage,” said Professor Wolf Reik, Babraham Institute group leader.

The Babraham Institute states:

In all mammals, the early embryo undergoes a number of molecular events just after fertilisation that set the stage for the rest of development. During this key ‘wake up call’ the genome of the embryo takes over control of the cell’s activities from the maternal genome. In humans, this happens at the 8-cell stage and is called zygotic genome activation (ZGA).

Before the findings of this study, investigating the details of human ZGA could only be done in human embryos; existing human stem cell models represented the embryo only at later stages of the developmental process. In the UK, experiments using embryos are permitted but highly regulated, meaning that research into early development relied in part on alternative, non-human models.

In 2012, cells representing the genome activation stage of development were found in mouse embryonic stem cells (ESCs), allowing researchers to learn more about mammalian ZGA. Almost a decade later, the Reik lab have found a human equivalent. The Reik lab’s discovery opens up a way to advance our knowledge of the earliest events during preimplantation development.

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