Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host–pathogen dynamics in lymphoblastoid cell lines

Lymphoblastoid cell lines (LCLs) are generated by transforming primary B cells with Epstein–Barr virus (EBV) and are used extensively as model systems in viral oncology, immunology, and human genetics research. In this study, we characterized single-cell transcriptomic profiles of five LCLs and pres...

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Autores principales: Elliott D SoRelle, Joanne Dai, Emmanuela N Bonglack, Emma M Heckenberg, Jeffrey Y Zhou, Stephanie N Giamberardino, Jeffrey A Bailey, Simon G Gregory, Cliburn Chan, Micah A Luftig
Formato: article
Lenguaje:EN
Publicado: eLife Sciences Publications Ltd 2021
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Acceso en línea:https://doaj.org/article/b49ae641f8704cfbb9d4caceb9a13345
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Sumario:Lymphoblastoid cell lines (LCLs) are generated by transforming primary B cells with Epstein–Barr virus (EBV) and are used extensively as model systems in viral oncology, immunology, and human genetics research. In this study, we characterized single-cell transcriptomic profiles of five LCLs and present a simple discrete-time simulation to explore the influence of stochasticity on LCL clonal evolution. Single-cell RNA sequencing (scRNA-seq) revealed substantial phenotypic heterogeneity within and across LCLs with respect to immunoglobulin isotype; virus-modulated host pathways involved in survival, activation, and differentiation; viral replication state; and oxidative stress. This heterogeneity is likely attributable to intrinsic variance in primary B cells and host–pathogen dynamics. Stochastic simulations demonstrate that initial primary cell heterogeneity, random sampling, time in culture, and even mild differences in phenotype-specific fitness can contribute substantially to dynamic diversity in populations of nominally clonal cells.