How cells use different strategies to respond to stress

Individual cells can respond in distinct ways to stress despite being genetically identical and in the same environment. This diversity may be key to responding to changes in the environment and ensuring cell survival.

This is what Dr. Francesc Posas and Dr. Laia de Nadal at IRB Barcelona have revealed in a study published in the journal Nature Communications. Headed by Dr. Mariona Nadal-Ribelles, the work has examined the stress response of yeast cells.

By analysing the genes that cells activate to adapt to stress, they discovered that each cell uses only some of these genes, thus generating diverse modular strategies.

Using advanced RNA sequencing techniques at the individual cell level, the researchers identified four distinct stress responses. Some cells activated genes associated with heat stress, others metabolic genes, while another group showed milder responses.

“The breakthrough in this study is that we demonstrate how the same cell population explores different strategies to respond to the same stress. Indeed, depending on the chosen strategy, cells can show more resistance to stress,” explains Dr. Posas.

Cells prepared for adverse conditions

A noteworthy observation was that cells activate genes related to stress even without external threats. These cells show slower growth in normal conditions but have a significant competitive advantage when real stress arises, adapting faster than others.

This behaviour resembles an evolutionary strategy that involves incurring an initial cost to increase the chances of survival under future adverse conditions. This phenomenon also points to a possible explanation of why some cells can survive medical treatments better than others.

Genetic factors that explain resistance

The team also identified several genetic factors that regulate the variability of stress genes. "These findings bring us closer to understanding the internal logic that governs cell response to stress and may contribute to shedding light on clinically relevant phenomena such as treatment resistance or rapid adaptation to environmental changes," says Dr. Nadal-Ribelles.

The study involved researchers from the University of Lausanne and the Institut Curie in Paris.

Related article:
Transcriptional heterogeneity shapes stress-adaptive responses in yeast
Mariona Nadal-Ribelles, Guillaume Lieb, Carme Solé, Yaima Matas, Ugo Szachnowski, Sara Andjus, Maria Quintana, Mònica Romo, Aitor Gonzalez Herrero, Antonin Morillon, Serge Pelet, Eulàlia de Nadal, Francesc Posas
Nature Communications (2025) DOI: 10.1038/s41467-025-57911-6