A conserved expression signature predicts growth rate and reveals cell & lineage-specific differences

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• dc.contributor.author Jiang, Zhisheng
• dc.contributor.author Generoso, Serena Francesca, 1988-
• dc.contributor.author Badia, Marta
• dc.contributor.author Payer, Bernhard
• dc.contributor.author Carey, Lucas, 1980-
• dc.date.accessioned 2022-04-01T09:19:29Z
• dc.date.available 2022-04-01T09:19:29Z
• dc.date.issued 2021
• dc.description.abstract Isogenic cells cultured together show heterogeneity in their proliferation rate. To determine the differences between fast and slow-proliferating cells, we developed a method to sort cells by proliferation rate, and performed RNA-seq on slow and fast proliferating subpopulations of pluripotent mouse embryonic stem cells (mESCs) and mouse fibroblasts. We found that slowly proliferating mESCs have a more naïve pluripotent character. We identified an evolutionarily conserved proliferation-correlated transcriptomic signature that is common to all eukaryotes: fast cells have higher expression of genes for protein synthesis and protein degradation. This signature accurately predicted growth rate in yeast and cancer cells, and identified lineage-specific proliferation dynamics during development, using C. elegans scRNA-seq data. In contrast, sorting by mitochondria membrane potential revealed a highly cell-type specific mitochondria-state related transcriptome. mESCs with hyperpolarized mitochondria are fast proliferating, while the opposite is true for fibroblasts. The mitochondrial electron transport chain inhibitor antimycin affected slow and fast subpopulations differently. While a major transcriptional-signature associated with cell-to-cell heterogeneity in proliferation is conserved, the metabolic and energetic dependency of cell proliferation is cell-type specific.
• dc.description.sponsorship This work has been funded by the Spanish Ministry of Science, Innovation and Universities (BFU2014-55275-P and BFU2017-88407-P to B.P. and BFU2015-68351-P to L.B.C.), the AXA Research Fund and the Agencia de Gestio d’Ajuts Universitaris i de Recerca (AGAUR, 2017 SGR 346 to B.P. and 2014 SGR 0974 & 2017 SGR 1054 to L.B.C.), the National Natural Science Foundation of China (31950410537 to L.B.C.). We would like to thank the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, to the ‘Centro de Excelencia Severo Ochoa’, and the Unidad de Excelencia María de Maeztu, funded by the MINECO (MDM-2014-0370). We also acknowledge the support of the CERCA Programme of the Generalitat de Catalunya. L.B.C. was supported by funding from Peking University and from the Peking-Tsinghua Center for Life Sciences, and from the Research Fund for International Young Scientists (National Natural Science Foundation of China)
• dc.format.mimetype application/pdf
• dc.identifier.citation Jiang Z, Generoso SF, Badia M, Payer B, Carey LB. A conserved expression signature predicts growth rate and reveals cell & lineage-specific differences. PLoS Comput Biol. 2021 Nov 11;17(11):e1009582. DOI: 10.1371/journal.pcbi.1009582
• dc.identifier.doi http://dx.doi.org/10.1371/journal.pcbi.1009582
• dc.identifier.issn 1553-734X
• dc.identifier.uri http://hdl.handle.net/10230/52812
• dc.language.iso eng
• dc.publisher Public Library of Science (PLoS)
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-55275-P
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68351-P
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-88407-P
• dc.rights © 2021 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.other Genètica
• dc.subject.other Proteïnes
• dc.subject.other Cèl·lules canceroses
• dc.title A conserved expression signature predicts growth rate and reveals cell & lineage-specific differences
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion