Embryo or placenta?
One and the same somatic cell during induction can turn into an embryonic (with the potential to give birth to fetal organs) or placental (with the potential for implantation and vascular growth) stem cell. A team of researchers led by Professor Yossi Buganim and Professor Tommy Kaplan from the Hebrew University in Jerusalem has identified 14,000 unique sites in DNA that together form the most elementary plan for creating embryos.
Induced pluripotent stem cells made from skin fibroblasts or other somatic cells using Yamanaki factors are identical to natural stem cells that develop at the earliest stages of embryogenesis and are responsible for the development of all fetal cells. However, they cannot create extraembryonic tissues, such as the placenta.
In 2015, Buganim and his colleagues were the first to grow artificial placental stem cells from skin cells. This step allowed scientists to create two of the earliest types of stem cells in the process of embryonic development, which occurs immediately after the sperm fertilizes the egg. In the new study, the team closely examined the changes that occur in skin cells during the transformation into embryonic or placental stem cells.
The researchers analyzed the changes that skin cells undergo in order to change their identity and become one of the two earliest types of stem cells – embryonic or placental. They compared gene expression, the availability and activity of DNA in the nucleus of a changing somatic cell, as well as epigenetic markers (that is, labels on DNA that are responsible for gene expression). All this is crucial when trying to transform a skin cell into an artificial embryonic or placental stem cell.
The authors found that the changes that occur during the transformation into embryonic or placental stem cells are completely different from each other at all levels, despite the fact that both were created from the same skin cells.
When the fibroblast turns into an artificial embryonic stem cell, the DNA regions responsible for the creation of the brain, heart and liver begin to reorganize and prepare for differentiation – with the right signal – into brain, heart or liver cells. On the other hand, when the same cells have been transformed into artificial placental stem cells, sections of DNA are rearranged, allowing the changing cell to implant and attract blood vessels – a phenomenon that occurs naturally when an embryo is implanted into the uterus.
The researchers compared the two processes in parallel and studied DNA methylation, which leads to suppression of gene expression. They found out that artificial placental stem cells contained about 14,000 methylated, that is, epigenetically disconnected, sections of DNA, and they were not in artificial embryonic stem cells. The team found that these DNA regions are responsible for the laying of all organs and cells in developing embryos – from the brain, heart, liver and kidneys to the skeleton, spinal cord and connective tissue.
In the future, this discovery will help to understand the embryo's defense system, which prevents the development of early placental cells into embryonic cells. Since placental cells are susceptible to damage and infection, the natural defense mechanism stops the migration of placental cells to the developing embryo and attachment to it to become part of the embryo. In general, this study highlights the key features of cell reprogramming and provides a powerful tool for studying cellular plasticity and making decisions about the fate of cells.
Article by M.Jaber et al. Comparative parallel multi-omics analysis during the induction of pluripotent and trophectoderm states is published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the American Friends of the Hebrew University website: Hebrew University Team Identifies Features to Reprogram Cells.