Cells of the future: possibility of targeted reprogramming

In order to transfer life from one cell to another, genetic information must be replicated using a process called DNA replication. This is not only done by the „copying“ of genetic information; rather, it requires a precise sequence of numerous molecular events. Researchers led by Prof Maria-Elena Torres-Padilla from Helmholtz Munich have recently uncovered a specific aspect of this process called „replication timing“ (RT) and its peculiarities in the emergence of new life. The new results have now been published in Nature.

The process of „replication timing“ (RT) of DNA refers to the specific times at which different sections of our genetic code are duplicated. Researchers at the Institute of Epigenetics and Stem Cells at Helmholtz Munich have implemented a technique called „Repli-seq“ to explore the close link between RT and the adaptive capacity of cells, cell plasticity. In addition, they were able to uncover a new link between replication timing and the process of how genes fold into three-dimensional structures within the cell nucleus.

Starting with the earliest developmental stage of an embryo, the zygote - the beginning of all life - scientists have created an RT map from this single-cell stage to the phase in which the embryo implants as a blastocyst in the mother. At the single-cell embryo stage, the RT is less structured, indicating flexible genome duplication in these early cells. After the four-cell stage, however, the RT becomes more defined. These changes in the RT correspond to the continuous changes in the DNA by proteins, the so-called chromatin marks, which indicate the activity of the genes and their significance for the functions of the cell.

Maria-Elena Torres-Padilla, last author of the study, explains: „The findings are remarkable and show us that the early embryonic cells have a very ‚flexible‘ programme for genome duplication. The early cells are also totipotent, which means that they can develop into every single cell in our body. What we have discovered could be the reason why these cells are able to generate all cell types in the body.“ The new findings on DNA replication open up possibilities for the targeted reprogramming of cells in the future. Dr Tsunetoshi Nakatani, first author of the study, adds: „We want to change cell identity in the future by converting a structured replication timing programme into a more flexible one.“

RNA polymerase, the enzyme that transcribes the genetic code of DNA into RNA, is an important player in the RT programme. With this knowledge, it will be possible to manipulate the RT in cells. The research team has discovered that the three-dimensional structure of the genome is formed first and only then is the RT programme established. This is an indication that the way in which our genome fits into the three-dimensional space of the cell nucleus has an influence on the flexibility of the RT programme.

In summary, the RT programme of DNA is a fascinating piece of the puzzle in the cycle of life. The precise process of genetic replication is closely linked to the ability of the cells of the early embryo to generate all cell types in our body. As research progresses, we are gaining a far-reaching understanding of the essential transmission of life, from cell to cell, from organism to organism, and of the ability of a cell to create a new body.

&about Helmholtz Munich

Helmholtz Munich is a cutting-edge biomedical research centre. Its mission is to develop groundbreaking solutions for a healthier society in a rapidly changing world. Interdisciplinary research teams focus on environmental diseases, in particular the treatment and prevention of diabetes, obesity, allergies and chronic lung diseases. Using artificial intelligence and bioengineering, the researchers transfer their findings to patients more quickly. Helmholtz Munich has more than 2,500 employees and is based in Munich/Neuherberg. It is a member of the Helmholtz Association, the largest scientific organisation in Germany with more than 43,000 employees and 18 research centres. More üabout Helmholtz Munich (Helmholtz Zentrum München German Research Centre for Environmental Health GmbH): www.helmholtz-munich.de

Source: Press release Helmholtz Zentrum München from 20.12.2023