The transcriptome dynamics of single cells during the cell cycle

Abstract The cell cycle is among the most basic phenomena in biology. Despite advances in single‐cell analysis, dynamics and topology of the cell cycle in high‐dimensional gene expression space remain largely unknown. We developed a linear analysis of transcriptome data which reveals that cells move...

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Main Authors: Daniel Schwabe, Sara Formichetti, Jan Philipp Junker, Martin Falcke, Nikolaus Rajewsky
Format: Article
Language:English
Published: Springer Nature 2020-11-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.15252/msb.20209946
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author Daniel Schwabe
Sara Formichetti
Jan Philipp Junker
Martin Falcke
Nikolaus Rajewsky
author_facet Daniel Schwabe
Sara Formichetti
Jan Philipp Junker
Martin Falcke
Nikolaus Rajewsky
author_sort Daniel Schwabe
collection DOAJ
description Abstract The cell cycle is among the most basic phenomena in biology. Despite advances in single‐cell analysis, dynamics and topology of the cell cycle in high‐dimensional gene expression space remain largely unknown. We developed a linear analysis of transcriptome data which reveals that cells move along a planar circular trajectory in transcriptome space during the cycle. Non‐cycling gene expression adds a third dimension causing helical motion on a cylinder. We find in immortalized cell lines that cell cycle transcriptome dynamics occur largely independently from other cellular processes. We offer a simple method (“Revelio”) to order unsynchronized cells in time. Precise removal of cell cycle effects from the data becomes a straightforward operation. The shape of the trajectory implies that each gene is upregulated only once during the cycle, and only two dynamic components represented by groups of genes drive transcriptome dynamics. It indicates that the cell cycle has evolved to minimize changes of transcriptional activity and the related regulatory effort. This design principle of the cell cycle may be of relevance to many other cellular differentiation processes.
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spelling doaj.art-ac0bf16148cd446cbdf40e2b7da6d7cb2024-10-28T09:17:03ZengSpringer NatureMolecular Systems Biology1744-42922020-11-01161112010.15252/msb.20209946The transcriptome dynamics of single cells during the cell cycleDaniel Schwabe0Sara Formichetti1Jan Philipp Junker2Martin Falcke3Nikolaus Rajewsky4Mathematical Cell Physiology, Max Delbrück Center for Molecular Medicine in the Helmholtz AssociationSystems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz AssociationQuantitative Developmental Biology, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz AssociationMathematical Cell Physiology, Max Delbrück Center for Molecular Medicine in the Helmholtz AssociationSystems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz AssociationAbstract The cell cycle is among the most basic phenomena in biology. Despite advances in single‐cell analysis, dynamics and topology of the cell cycle in high‐dimensional gene expression space remain largely unknown. We developed a linear analysis of transcriptome data which reveals that cells move along a planar circular trajectory in transcriptome space during the cycle. Non‐cycling gene expression adds a third dimension causing helical motion on a cylinder. We find in immortalized cell lines that cell cycle transcriptome dynamics occur largely independently from other cellular processes. We offer a simple method (“Revelio”) to order unsynchronized cells in time. Precise removal of cell cycle effects from the data becomes a straightforward operation. The shape of the trajectory implies that each gene is upregulated only once during the cycle, and only two dynamic components represented by groups of genes drive transcriptome dynamics. It indicates that the cell cycle has evolved to minimize changes of transcriptional activity and the related regulatory effort. This design principle of the cell cycle may be of relevance to many other cellular differentiation processes.https://doi.org/10.15252/msb.20209946cell biologycell cycledynamical systemssingle‐cell RNA sequencingsystems biology
spellingShingle Daniel Schwabe
Sara Formichetti
Jan Philipp Junker
Martin Falcke
Nikolaus Rajewsky
The transcriptome dynamics of single cells during the cell cycle
Molecular Systems Biology
cell biology
cell cycle
dynamical systems
single‐cell RNA sequencing
systems biology
title The transcriptome dynamics of single cells during the cell cycle
title_full The transcriptome dynamics of single cells during the cell cycle
title_fullStr The transcriptome dynamics of single cells during the cell cycle
title_full_unstemmed The transcriptome dynamics of single cells during the cell cycle
title_short The transcriptome dynamics of single cells during the cell cycle
title_sort transcriptome dynamics of single cells during the cell cycle
topic cell biology
cell cycle
dynamical systems
single‐cell RNA sequencing
systems biology
url https://doi.org/10.15252/msb.20209946
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