Partitioning stable and unstable expression level variation in cell populations: A theoretical framework and its application to the T cell receptor
Open Access
- 1 August 2020
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Computational Biology
- Vol. 16 (8), e1007910
- https://doi.org/10.1371/journal.pcbi.1007910
Abstract
Phenotypic variation in the copy number of gene products expressed by cells or tissues has been the focus of intense investigation. To what extent the observed differences in cellular expression levels are persistent or transient is an intriguing question. Here, we develop a quantitative framework that resolves the expression variation into stable and unstable components. The difference between the expression means in two cohorts isolated from any cell population is shown to converge to an asymptotic value, with a characteristic time,tau(T), that measures the timescale of the unstable dynamics. The asymptotic difference in the means, relative to the initial value, measures the stable proportion of the original population varianceR alpha 2. Empowered by this insight, we analysed the T-cell receptor (TCR) expression variation in CD4 T cells. About 70% of TCR expression variance is stable in a diverse polyclonal population, while over 80% of the variance in an isogenic TCR transgenic population is volatile. In both populations the TCR levels fluctuate with a characteristic time of 32 hours. This systematic characterisation of the expression variation dynamics, relying on time series of cohorts' means, can be combined with technologies that measure gene or protein expression in single cells or in bulk.Keywords
Funding Information
- Fundação para a Ciência e Tecnologia (SFRH/BD/33572/2008, PTDC/BIA-BCM/108020/2008)
- Fundação para a Ciência e Tecnologia (SFRH/BD/33572/2008, PTDC/BIA-BCM/108020/2008)
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