A research team at the Max Planck Institute for Molecular Genetics in Berlin has explored the role of factors in embryonic development that do not alter the DNA sequence, but only modify its epigenetics “packaging”;. In the scientific journal nature, they describe how regulatory mechanisms contribute to the formation of various tissues and organs in early mouse embryos.
A fertilized egg cell develops into a complete organism with a host of different tissues and organs, although the genetic information is exactly the same in each cell. A complex clock of molecules regulates which cell in the body fulfills each task and determines the right time and place to activate each gene.
Epigenetic regulatory factors are part of this molecular mechanism and act to modify the “packaging” of the DNA molecule without altering the underlying genetic information. Specifically, they act to mark DNA and control which parts can be accessed in each cell.
Most of these regulators are essential, and embryos that lack them tend to die during the time of development when organs begin to emerge. However, these regulators can have specific functions that vary in each cell, making them difficult to study. This has also been a major obstacle to the study of these proteins, which are not only important for embryonic development but also involved in cancer formation.
Detailed examination of embryos
“The same regulator is present in all cells, but it can have very different tasks, depending on the cell type and the time of development,” says Stefanie Grosswendt, one of the first authors of a new study in the scientific journal nature.
Grosswendt and her colleague Helene Kretzmer from the Alexander Meissner Laboratory at the Max Planck Institute for Molecular Genetics (MPIMG) in Berlin together with Zachary Smith from Harvard University, MA, have now managed to clarify the importance of epigenetic regulators for precise embryonic development. unprecedented.
The researchers analyzed ten of the most important epigenetic regulators. Using the CRISPR-Cas9 system, they first specifically removed genes encoding regulatory factors in fertilized oocytes and then observed the effects on embryo development days later.
After the embryos had developed for about six to nine days, the team examined the anatomical and molecular changes that resulted from the lack of proper regulator. They found that the cellular composition of many of the embryos was substantially altered. Cells of certain species existed in excessive numbers, while others were not produced at all.
By analyzing thousands of individual cells
To understand these changes at a molecular level, the researchers examined hundreds to thousands of individual cells from embryos, from which single epigenetic regulators had been systematically removed. They sequenced RNA molecules from almost 280,000 individual cells to investigate the consequences of loss of function. RNA transmits information encoded in DNA, allowing researchers to understand the identity and behavior of cells using sequence technologies.
In their analysis, the scientists focused on a stage of development in which epigenetic regulators are particularly important. When they compared the data of altered and unchanged embryos, they identified genes that were disordered, and cell types that are abnormally redundant or unproductive. From this overview, they derived previously unknown functions of many epigenetic regulators.
Complex effects during development
An eight-day-old mouse embryo looks a bit like a sea and has no organs yet. “From the appearance of an early embryo, one can often guess which structures and organs will form and which will not,” say bioinformatics Helene Kretzmer and biologist Zachary Smith, who are also the first authors of the publication. “Our sequencing allows for a much more accurate, high-resolution view.”
The single-cell analysis gave them a fairly detailed picture during the first nine days of mouse development. Often, turning off a single regulator led to growth effects throughout the interactive gene network, with many different activated or inactivated genes during the course of development.
The removal of the Polycomb epigenetic regulator (PRC2) had a particularly remarkable impact. “Without PRC2, the embryo looks egg-shaped and very small after eight and a half days, which is very unusual,” says Kretzmer. “We see big changes in how DNA is packaged that happens much earlier, long before the embryo develops morphological abnormalities.”
The researchers found that PRC2 is responsible for limiting the amount of gin birth cells – cells that later become sperm and eggs. Without PRC2, the embryo develops an excessive number of these cells, loses its shape and dies after a short time.
Starting point for further analysis
“With the combination of new technologies we addressed issues that have been in the air for 25 years,” says Alexander Meissner, who led the study. “We now better understand how epigenetic regulators regulate many different cell types in the body.”
The work is only the first step to even more detailed investigations, says Meissner. “Our method allows us to investigate other factors, such as transcription or growth factors, or even a combination of these. Now we are able to observe the early stages of development at a level of detail that was previously unimaginable. ”
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Stefanie Grosswendt et al. The function of the epigenetic regulator through mouse gastrulation, nature (2020). DOI: 10.1038 / s41586-020-2552-x
Provided by the Max Planck Society
citation: Epigenetics and cell diversity in embryo (2020, July 30) Retrieved July 31, 2020 from https://phys.org/news/2020-07-epigenetics-cell-diversity-embryo.html
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