Control of tissue development and cell diversity by cell cycle dependent transcriptional filtering

Abstract
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Abstract

Cell cycle duration changes dramatically during development, starting out fast to generate cells quickly and slowing down over time as the organism matures. The cell cycle can also act as a transcriptional filter to control the expression of long gene transcripts which are partially transcribed in short cycles. Using mathematical simulations of cell proliferation, we identify an emergent property, that this filter can act as a tuning knob to control gene transcript expression, cell diversity and the number and proportion of different cell types in a tissue. Our predictions are supported by comparison to single-cell RNA-seq data captured over embryonic development. Additionally, evolutionary genome analysis shows that fast developing organisms have a narrow genomic distribution of gene lengths while slower developers have an expanded number of long genes. Our results support the idea that cell cycle dynamics may be important across multicellular animals for controlling gene transcript expression and cell fate.

Data availability

All data generated during this study are included in the manuscript and supporting files. Source file for the code is available athttps://github.com/BaderLab/Cell_Cycle_Theory

The following previously published data sets were used

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Author details

Maria Abou Chakra

The Donnelly Centre, University of Toronto, Toronto, Canada

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4895-954X
Ruth Isserlin

The Donnelly Centre, University of Toronto, Toronto, Canada

Competing interests
The authors declare that no competing interests exist.
Thinh N. Tran

The Donnelly Centre, University of Toronto, Toronto, Canada

Competing interests
The authors declare that no competing interests exist.
Gary D Bader

The Donnelly Centre, University of Toronto, Toronto, Canada

For correspondence
gary.bader@utoronto.ca

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0185-8861

Funding

Canada First Research Excellence Fund

Gary D Bader

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.