Zurich – For the first time, researchers at the University of Zurich (UZH) can follow live how cellular heterogeneity develops. They discovered that DNA damage and stress also have long-term effects on cellular diversity. This makes tumors more complex, for example, or can reduce the effectiveness of therapies.
(CONNECT) Researchers at UZH have investigated how diversity arises in cell populations. According to a UZH report, this diversity can lead to diseases such as cancer, making tumors more complex and therapies less effective. For this reason, the team wanted to understand more precisely what leads to diversity and whether and how it is expressed across cell generations. To this end, it has developed a method that allows these processes to be followed in detail and in real time under the microscope for the first time.
Using CRISPR-based genome editing, they attached fluorescent labels to two proteins: one to track the DNA duplication process and one to mark acquired DNA damage. “We were able to observe how cancer cells react to various stress factors over several cell generations and how this increases heterogeneity within the cell population,” explains Merula Stout, UZH doctoral student at the Institute of Molecular Mechanisms in Disease and co-first author of the study.
They also investigated the extent of different stress signals in daughter and grandchild cells. As they saw, the observed differences continued in the next cell generation. “DNA damage and stress therefore not only have a short-term effect, but also long-term effects on cellular diversity,” says UZH. The team also found that multiple genome copies promote resistance to therapy.
The aim now is to further expand and automate the method in collaboration with the UZH technology platforms. Because “we are very likely only seeing the proverbial tip of the iceberg at the moment,” says Matthias Altmeyer, head of the study and UZH professor. ce/mm
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