UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology; Graduate School of Biomedical Sciences

Publication Date

2021-01-27

Document Type

Article

Disciplines

Cell Biology | Immunology and Infectious Disease | Microbiology | Nucleic Acids, Nucleotides, and Nucleosides | Systems Biology | Viruses

Abstract

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.

Keywords

B-cell differentiation, Epstein-Barr virus, NFkappaB, human, immunology, infectious disease, inflammation, lymphoblastoid cell lines, microbiology, systems modeling, virus, virus infection

Rights and Permissions

Copyright © 2021, SoRelle et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

DOI of Published Version

10.7554/eLife.62586

Source

SoRelle ED, Dai J, Bonglack EN, Heckenberg EM, Zhou JY, Giamberardino SN, Bailey JA, Gregory SG, Chan C, Luftig MA. Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host-pathogen dynamics in lymphoblastoid cell lines. Elife. 2021 Jan 27;10:e62586. doi: 10.7554/eLife.62586. PMID: 33501914; PMCID: PMC7867410. Link to article on publisher's site

Journal/Book/Conference Title

eLife

Related Resources

Link to Article in PubMed

PubMed ID

33501914

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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