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Transcriptional heterogeneity shapes stress-adaptive responses in yeast

Title: Transcriptional heterogeneity shapes stress-adaptive responses in yeast
Authors: Nadal Ribelles, Mariona; Lieb, Guillaume; Sole Serra, Carme; Matas, Yaima; Szachnowski, Ugo; Andjus, Sara; Quintana Verdaguer, Maria; Romo, Mónica; Gonzalez Herrero, Aitor; Morillon, Antonin; Pelet, Serge; Nadal Clanchet, Eulàlia De; Posas, Francesc
Source: Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
Publisher Information: Springer Nature
Publication Year: 2025
Collection: Dipòsit Digital de la Universitat de Barcelona
Subject Terms: Estrès (Fisiologia); Transcripció genètica; Stress (Physiology); Genetic transcription
Description: In response to stress, cells activate signaling pathways that coordinate broad changes in gene expression to enhance cell survival. Remarkably, complex variations in gene expression occur even in isogenic populations and in response to similar signaling inputs. However, the molecular mechanisms underlying this variability and their influence on adaptive cell fate decisions are not fully understood. Here, we use scRNA-seq to longitudinally assess transcriptional dynamics during osmoadaptation in yeast. Our findings reveal highly heterogeneous expression of the osmoresponsive program, which organizes into combinatorial patterns that generate distinct cellular programs. The induction of these programs is favored by global transcriptome repression upon stress. Cells displaying basal expression of the osmoresponsive program are hyper-responsive and resistant to stress. Through a transcription-focused analysis of more than 300 RNA-barcoded deletion mutants, we identify genetic factors that shape the heterogeneity of the osmostress-induced transcriptome, define regulators of stress-related subpopulations and find a link between transcriptional heterogeneity and increased cell fitness. Our findings provide a regulatory map of the complex transcriptional phenotypes underlying osmoadaptation in yeast and highlight the importance of transcriptional heterogeneity in generating distinct adaptive strategies.
Document Type: article in journal/newspaper
File Description: 17 p.; application/pdf
Language: English
Relation: Reproducció del document publicat a: https://doi.org/10.1038/s41467-025-57911-6; Nature Communications, 2025, vol. 16; https://doi.org/10.1038/s41467-025-57911-6; https://hdl.handle.net/2445/219972; 6728773
Availability: https://hdl.handle.net/2445/219972
Rights: cc-by (c) Nadal Ribelles, Mariona et al., 2025 ; http://creativecommons.org/licenses/by/3.0/es/ ; info:eu-repo/semantics/openAccess
Accession Number: edsbas.96310C37
Database: BASE