Instytut Podstawowych Problemów Techniki
Polskiej Akademii Nauk

Partnerzy

Christopher Clark


Ostatnie publikacje
1.  Bagnall J., Rowe W., Alachkar N., Roberts J., England H., Clark C., Platt M., Jackson Dean A., Muldoon M., Paszek P., Gene-Specific Linear Trends Constrain Transcriptional Variability of the Toll-like Receptor Signaling, Cell Systems, ISSN: 2405-4712, DOI: 10.1016/j.cels.2020.08.007, Vol.11, No.3, pp.300-314, 2020

Streszczenie:
Single-cell gene expression is inherently variable, but how this variability is controlled in response to stimulation remains unclear. Here, we use single-cell RNA-seq and single-molecule mRNA counting (smFISH) to study inducible gene expression in the immune toll-like receptor system. We show that mRNA counts of tumor necrosis factor α conform to a standard stochastic switch model, while transcription of interleukin-1β involves an additional regulatory step resulting in increased heterogeneity. Despite different modes of regulation, systematic analysis of single-cell data for a range of genes demonstrates that the variability in transcript count is linearly constrained by the mean response over a range of conditions. Mathematical modeling of smFISH counts and experimental perturbation of chromatin state demonstrates that linear constraints emerge through modulation of transcriptional bursting along with gene-specific relationships. Overall, our analyses demonstrate that the variability of the inducible single-cell mRNA response is constrained by transcriptional bursting.

Słowa kluczowe:
cellular heterogeneity, transcriptional bursting, stochastic gene expression, toll-like receptor, single-cell transcriptomics, stochastic modeling, TNF-α, IL-1β

Afiliacje autorów:
Bagnall J. - inna afiliacja
Rowe W. - inna afiliacja
Alachkar N. - inna afiliacja
Roberts J. - inna afiliacja
England H. - inna afiliacja
Clark C. - inna afiliacja
Platt M. - inna afiliacja
Jackson Dean A. - inna afiliacja
Muldoon M. - inna afiliacja
Paszek P. - inna afiliacja
200p.

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