Patterns of interdivision time correlations reveal hidden cell cycle factors
- Imperial College London, United Kingdom
- MRC London Institute of Medical Sciences, United Kingdom
Abstract
The time taken for cells to complete a round of cell division is a stochastic process controlled, in part, by intracellular factors. These factors can be inherited across cellular generations which gives rise to, often non-intuitive, correlation patterns in cell cycle timing between cells of different family relationships on lineage trees. Here, we formulate a framework of hidden inherited factors affecting the cell cycle that unifies known cell cycle control models and reveals three distinct interdivision time correlation patterns: aperiodic, alternator and oscillator. We use Bayesian inference with single-cell datasets of cell division in bacteria, mammalian and cancer cells, to identify the inheritance motifs that underlie these datasets. From our inference, we find that interdivision time correlation patterns do not identify a single cell cycle model but generally admit a broad posterior distribution of possible mechanisms. Despite this unidentifiability, we observe that the inferred patterns reveal interpretable inheritance dynamics and hidden rhythmicity of cell cycle factors. This reveals that cell cycle factors are commonly driven by circadian rhythms, but their period may differ in cancer. Our quantitative analysis thus reveals that correlation patterns are an emergent phenomenon that impact cell proliferation and these patterns may be altered in disease.
Data availability
The current manuscript is a computational study, so no data have been generated for this manuscript. Modelling code is uploaded to gitHub https://github.com/fernhughes/Lineage-tree-correlation-pattern-inference.
-
Research data supporting Cell size control driven by the circadian clock and environment in cyanobacteriaApollo - University of Cambridge Repository.
-
Supplementary Data 2 supporting Hidden heterogeneity and circadian-controlled cell fate inferred from single cell lineagesNature Communications, Supplementary Data.
-
Mycobacteria Modify Their Cell Size Control under Sub-Optimal Carbon SourcesMiles Priestman shared the raw data.
Article and author information
Author details
Funding
EPSRC Centre for Mathematics of Precision Healthcare (EP/N014529/1)
- Fern A Hughes
MRC London Institute of Medical Sciences (MC-A658-5TY60)
- Alexis Barr
UKRI Future Leaders Fellowship (MR/T018429/1)
- Philipp Thomas
CRUK Career Development Fellowship (C63833/A25729)
- Alexis Barr
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Arvind Murugan, University of Chicago, United States
Publication history
- Received: June 9, 2022
- Preprint posted: June 28, 2022 (view preprint)
- Accepted: November 14, 2022
- Accepted Manuscript published: November 15, 2022 (version 1)
- Version of Record published: January 6, 2023 (version 2)
Copyright
© 2022, Hughes et al.
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.
Metrics
-
- 917
- Page views
-
- 163
- Downloads
-
- 0
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Patterns of interdivision time correlations reveal hidden cell cycle factors
eLife 11:e80927.
https://doi.org/10.7554/eLife.80927
Further reading
-
- Cell Biology
- Neuroscience
Neurons form dense neural circuits by connecting to each other via synapses and exchange information through synaptic receptors to sustain brain activities. Excitatory postsynapses form and mature on spines composed predominantly of actin, while inhibitory synapses are formed directly on the shafts of dendrites where both actin and microtubules (MTs) are present. Thus, it is the accumulation of specific proteins that characterizes inhibitory synapses. In this study, we explored the mechanisms that enable efficient protein accumulation at inhibitory postsynapse. We found that some inhibitory synapses function to recruit the plus end of MTs. One of the synaptic organizers, Teneurin-2 (TEN2), tends to localize to such MT-rich synapses and recruits MTs to inhibitory postsynapses via interaction with MT plus-end tracking proteins EBs. This recruitment mechanism provides a platform for the exocytosis of GABAA receptors. These regulatory mechanisms could lead to a better understanding of the pathogenesis of disorders such as schizophrenia and autism, which are caused by excitatory/inhibitory (E/I) imbalances during synaptogenesis.
-
- Cell Biology
Different anatomical locations of the body skin show differences in their gene expression patterns depending on different origins, and the inherent heterogeneous information can be maintained in adults. However, highly resolvable cellular specialization is less well characterized in different anatomical regions of the skin. Pig is regarded as an excellent model animal for human skin research in view of its similar physiology to human. In this study, single-cell RNA sequencing was performed on pig skin tissues from six different anatomical regions of Chenghua (CH) pigs, with a superior skin thickness trait, and the back site of large white (LW) pigs. We obtained 233,715 cells, representing seven cell types, among which we primarily characterized the heterogeneity of the top three cell types, including smooth muscle cells (SMCs), endothelial cells (ECs), and fibroblasts (FBs). Then, we further identified several subtypes of SMCs, ECs, and FBs, and discovered the expression patterns of site-specific genes involved in some important pathways such as the immune response and extracellular matrix (ECM) synthesis in different anatomical regions. By comparing differentially expressed genes of skin FBs among different anatomical regions, we considered TNN, COL11A1, and INHBA as candidate genes for facilitating ECM accumulation. These findings of heterogeneity in the main skin cell types from different anatomical sites will contribute to a better understanding of inherent skin information and place the potential focus on skin generation, transmission, and transplantation, paving the foundation for human skin priming.
