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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Bibliographic Details
Published in:eLife 2021-01, Vol.10
Main Authors: SoRelle, Elliott D, Dai, Joanne, Bonglack, Emmanuela N, Heckenberg, Emma M, Zhou, Jeffrey Y, Giamberardino, Stephanie N, Bailey, Jeffrey A, Gregory, Simon G, Chan, Cliburn, Luftig, Micah A
Format: Article
Language:English
Subjects:
B-cell differentiation
B-Lymphocytes - physiology
Cell culture
Cell cycle
Cell Line
Epstein-Barr virus
Gene expression
Herpesvirus 4, Human - physiology
Host-Pathogen Interactions
Humans
Immunoglobulins
Immunology and Inflammation
Infections
Lymphoblastoid cell lines
Lymphocytes B
Microbiology and Infectious Disease
NFkappaB
Oxidative stress
Pathogens
Phenotypes
Proteins
RNA-Seq
Single-Cell Analysis
Statistical sampling
Stochasticity
systems modeling
Transcriptome
Transcriptomics
virus infection
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.62586