Computer simulations visualize how DNA converts cells into stem cells, Researchers have discovered how major proteins help activate DNA genomes during the conversion of ordinary human cells into adult stem cells.
Cell identity is determined by where DNA is “read” or “unread” at a certain point in time. Transmission of signals in cells to start or stop DNA reading occurs through proteins, called transcription factors.
Changes in identity naturally occur during development when cells move from cells that are not assigned to certain cell types. Apparently, this transition can also be reversed. Now the Computer simulations visualize how DNA converts cells into stem cells.
In 2012, Japanese researchers were awarded the Nobel Prize for pushing ordinary skin cells back to stem cells.
It is not yet known how skin cells are converted to stem cells right at the molecular scale. “A comprehensive understanding of the atomic breakdown process is very important if we want to produce these cells reliably and efficiently for each patient in the future,” the researcher said.
It is believed that this type of cell manipulation could be part of the solution for diseases such as Alzheimer’s and Parkinson’s in the future, but the manufacturing process must be more efficient and predictable. Computer simulations visualize how DNA converts cells into stem cells.
One of the main proteins involved in stem cell production is a transcription factor called Oct4. This induces gene expression or protein activity that is “null” adult cells in stem cells.
This induced gene is not active in mature cells and is in a tightly closed state of chromatin, the structure that stores DNA in the nucleus.
Oct4 contributes to the opening of chromatin to allow gene expression. For this reason, Oct4 is known as a pioneering transcription factor.
Data from Kozhokaru and his doctoral students – and lead author of the publication – Jan Huertas shows how Oct4 binds DNA to what is called a nucleosome, a repetitive core structure in chromatin.
Molecules consist of two domains, only one of which can bind to a specific DNA sequence in the nucleosome at this stage of the process. With our simulations, we discover which configurations are stable and how the dynamics of nucleosomes affect Oct4 binding.
This is the first time that computer simulations have shown how pioneering transcription factors bind nucleosomes to open chromatin and regulate gene expression. Our computational approach to obtaining the Oct4 model can also be used to look for other transcription factors and understand how they bind to nucleosomes, the researchers said. Computer simulations visualize how DNA converts cells into stem cells.
Cojocaru also wants to improve the current Oct4 model to provide the final structure for the Oct4 nucleosome complex. “We have known for almost 15 years that Oct4, along with three other pioneering factors, convert adult cells into stem cells.
However, we still do not know how their performance is. Defining experimental structures for such a system is very expensive and time-consuming. We want to get the final model for binding Oct4 to the nucleosome by combining computer simulations with various laboratory experiments.
Hopefully, our final model will enable us to develop pioneering transcription factors for the efficient and reliable production of stem cells and other cells needed in regenerative medicine.