New stem cell population provides a new way to study the awakening of
the human genome
Cells resembling the 8-cell embryo will help researchers advance our
knowledge of the earliest events in development

Date:
February 24, 2022
Source:
Babraham Institute
Summary:
Researchers have discovered a new type of stem cell that resembles
cells in the early human embryo during the transition of 'genomic
power' from mother to embryo. During this major developmental event
the genome is reset and reorganized with large numbers of embryonic
genes being expressed for the first time. If unsuccessful, further
embryo development fails or there may be implications for later
developmental stages. The newly identified stem cells provide the
closest model available to study this process without the need
for human embryos. This model of the early embryo will allow the
study of human genome activation in a much more detailed way,
providing important functional insights into genome regulation,
developmental disorders, and early embryo loss.



FULL STORY ========================================================================== Researchers from the Babraham Institute have today published their
latest work in the journal Cell Stem Celldescribing 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. 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.


==========================================================================
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
at the Institute have found a human equivalent. The lab's discovery
opens up a way to advance our knowledge of the earliest events during preimplantation development.

Dr Jasmin Taubenschmid-Stowers, lead author and Research Fellow in
the Reik lab, part of the Institute's Epigenetics research programme , commented: "Studying mouse embryonic stem cells has allowed researchers to learn about the general process of genome activation, but we could learn
even more about this important step in human development thanks to our discovery of a human stem cell counterpart." In order to function, cells
take copies of the genome in the form of an RNA code which is translated
into proteins. The RNA code output is called the transcriptome and it
can be used to identify different populations of cells. In this study, researchers used existing human data sets and information from mouse
ESC studies to identify characteristic transcriptome marks that could be
linked to genome activation. Using single cell techniques, they started
the search for similar cells in their population of human ESCs.

The team found a subset of human ESCs with the right transcriptome marks
to be a potential match for the 8-cell stage, when the major wave of
genome activation occurs. They called these cells '8-cell like cells' or
8CLCs and used the published human data to further validate and confirm
that these cells shared the same molecular outputs indicative of genome activation and could be pursued as a reliable model for future studies.

To further explore the extent of the similarities between their 8CLCs and
8- cell stage in human embryos, the team worked with Professor Jennifer
Nichols from the Wellcome -- MRC Cambridge Stem Cell Institute. Together
they were able to select and search for proteins present in both sets
of cells that were indicative of ZGA. Their results showed that the ZGA-associated proteins of 8CLCs closely matched those seen in human
8-cell embryos.

As Jasmin explains: "The collaboration with Professor Nichols and her team
was vital as we could identify selected proteins and really look at those
in real, fixed human 8-cell stage embryo cells compared to our new stem
cell counterparts. This work confirmed that our 8C-like cells matched
at the protein level too, in additional to the transcriptomics data,
providing validation that the 8-cell like cells matched embryo cells
across multiple molecular layers." "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.

========================================================================== Story Source: Materials provided by Babraham_Institute. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Jasmin Taubenschmid-Stowers, Maria Rostovskaya, Fa'tima Santos,
Sebastian
Ljung, Ricard Argelaguet, Felix Krueger, Jennifer Nichols, Wolf
Reik. 8C- like cells capture the human zygotic genome activation
program in vitro.

Cell Stem Cell, 2022; DOI: 10.1016/j.stem.2022.01.014 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220224112650.htm

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