A conserved expression signature predicts growth rate and reveals cell & lineage-specific differences.
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...
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2021
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oai:doaj.org-article:10db488fa4ed49b68a9a22351a3c0d9c2021-12-02T19:58:12ZA conserved expression signature predicts growth rate and reveals cell & lineage-specific differences.1553-734X1553-735810.1371/journal.pcbi.1009582https://doaj.org/article/10db488fa4ed49b68a9a22351a3c0d9c2021-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009582https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Isogenic 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.Zhisheng JiangSerena F GenerosoMarta BadiaBernhard PayerLucas B CareyPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 11, p e1009582 (2021) |
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Biology (General) QH301-705.5 |
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Biology (General) QH301-705.5 Zhisheng Jiang Serena F Generoso Marta Badia Bernhard Payer Lucas B Carey A conserved expression signature predicts growth rate and reveals cell & lineage-specific differences. |
description |
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. |
format |
article |
author |
Zhisheng Jiang Serena F Generoso Marta Badia Bernhard Payer Lucas B Carey |
author_facet |
Zhisheng Jiang Serena F Generoso Marta Badia Bernhard Payer Lucas B Carey |
author_sort |
Zhisheng Jiang |
title |
A conserved expression signature predicts growth rate and reveals cell & lineage-specific differences. |
title_short |
A conserved expression signature predicts growth rate and reveals cell & lineage-specific differences. |
title_full |
A conserved expression signature predicts growth rate and reveals cell & lineage-specific differences. |
title_fullStr |
A conserved expression signature predicts growth rate and reveals cell & lineage-specific differences. |
title_full_unstemmed |
A conserved expression signature predicts growth rate and reveals cell & lineage-specific differences. |
title_sort |
conserved expression signature predicts growth rate and reveals cell & lineage-specific differences. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doaj.org/article/10db488fa4ed49b68a9a22351a3c0d9c |
work_keys_str_mv |
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1718375764097761280 |