Transcriptional heterogeneity shapes stress-adaptive responses in yeast

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 unde...

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Autores: Nadal Ribelles, Mariona, 1984-, Lieb, Guillaume, Solé, Carme, Matas, Yaima, Szachnowski, Ugo, Andjus, Sara, Quintana, Maria, Romo, Mònica, Gonzalez Herrero, Aitor, Morillon, Antonin, Pelet, Serge, Nadal Clanchet, Eulàlia de, Posas Garriga, Francesc
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/70329
Acceso en línea:http://hdl.handle.net/10230/70329
http://dx.doi.org/10.1038/s41467-025-57911-6
Access Level:acceso abierto
Palabra clave:Gene expression
RNA
Transcription
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oai_identifier_str oai:recercat.cat:10230/70329
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network_name_str España
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dc.title.none.fl_str_mv Transcriptional heterogeneity shapes stress-adaptive responses in yeast
title Transcriptional heterogeneity shapes stress-adaptive responses in yeast
spellingShingle Transcriptional heterogeneity shapes stress-adaptive responses in yeast
Nadal Ribelles, Mariona, 1984-
Gene expression
RNA
Transcription
title_short Transcriptional heterogeneity shapes stress-adaptive responses in yeast
title_full Transcriptional heterogeneity shapes stress-adaptive responses in yeast
title_fullStr Transcriptional heterogeneity shapes stress-adaptive responses in yeast
title_full_unstemmed Transcriptional heterogeneity shapes stress-adaptive responses in yeast
title_sort Transcriptional heterogeneity shapes stress-adaptive responses in yeast
dc.creator.none.fl_str_mv Nadal Ribelles, Mariona, 1984-
Lieb, Guillaume
Solé, Carme
Matas, Yaima
Szachnowski, Ugo
Andjus, Sara
Quintana, Maria
Romo, Mònica
Gonzalez Herrero, Aitor
Morillon, Antonin
Pelet, Serge
Nadal Clanchet, Eulàlia de
Posas Garriga, Francesc
author Nadal Ribelles, Mariona, 1984-
author_facet Nadal Ribelles, Mariona, 1984-
Lieb, Guillaume
Solé, Carme
Matas, Yaima
Szachnowski, Ugo
Andjus, Sara
Quintana, Maria
Romo, Mònica
Gonzalez Herrero, Aitor
Morillon, Antonin
Pelet, Serge
Nadal Clanchet, Eulàlia de
Posas Garriga, Francesc
author_role author
author2 Lieb, Guillaume
Solé, Carme
Matas, Yaima
Szachnowski, Ugo
Andjus, Sara
Quintana, Maria
Romo, Mònica
Gonzalez Herrero, Aitor
Morillon, Antonin
Pelet, Serge
Nadal Clanchet, Eulàlia de
Posas Garriga, Francesc
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Gene expression
RNA
Transcription
topic Gene expression
RNA
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.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/70329
http://dx.doi.org/10.1038/s41467-025-57911-6
http://hdl.handle.net/10230/70329
url http://hdl.handle.net/10230/70329
http://dx.doi.org/10.1038/s41467-025-57911-6
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nat Commun. 2025 Mar 17;16(1):2631
info:eu-repo/grantAgreement/ES/3PE/PID2021-124723NB-C21
info:eu-repo/grantAgreement/ES/3PE/PID2021-124723NB-C22
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
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application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
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spelling Transcriptional heterogeneity shapes stress-adaptive responses in yeastNadal Ribelles, Mariona, 1984-Lieb, GuillaumeSolé, CarmeMatas, YaimaSzachnowski, UgoAndjus, SaraQuintana, MariaRomo, MònicaGonzalez Herrero, AitorMorillon, AntoninPelet, SergeNadal Clanchet, Eulàlia dePosas Garriga, FrancescGene expressionRNATranscriptionIn 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.This work was funded by: PID2021-124723NB-C21/C22 funded by MICIU/AEI /10.13039/501100011033 and ERDF/EU to F.P. and E.dN. Funding from the Ministry of Science, Innovation and Universities through the Centres of Excellence Severo Ochoa Award, and from the CERCA Programme of the Government of Catalonia and the Unidad de Excelencia María de Maeztu, funded by the AEI (CEX2018-000792-M). The Ramon y Cajal Program (Spanish Ministry of Science, RYC2021-033520-I) and La Caixa Junior (LCF/BQ/PR20/11770001) awarded to M.N.R. F.P. and E.deN. are recipients of an ICREA Acadèmia award (Government of Catalonia). The La Caixa Retaining PhD (LCF/BQ/DR21/11880014) to M.Q. S.A. was funded with EMBO Scientific Exchange Grant Number 9387. Work in the Pelet lab was supported by the University of Lausanne and the Swiss National Science Foundation (Grant # 31003A 182431).Nature Research202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/70329http://dx.doi.org/10.1038/s41467-025-57911-6http://hdl.handle.net/10230/70329reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNat Commun. 2025 Mar 17;16(1):2631info:eu-repo/grantAgreement/ES/3PE/PID2021-124723NB-C21info:eu-repo/grantAgreement/ES/3PE/PID2021-124723NB-C22© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/703292026-05-29T05:05:01Z
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