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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/62586 |
| _version_ | 1811253643404378112 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Elliott D SoRelle |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T16:54:06Z |
| format | Article |
| id | doaj.art-b49ae641f8704cfbb9d4caceb9a13345 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:54:06Z |
| publishDate | 2021-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b49ae641f8704cfbb9d4caceb9a133452022-12-22T03:24:18ZengeLife Sciences Publications LtdeLife2050-084X2021-01-011010.7554/eLife.62586Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host–pathogen dynamics in lymphoblastoid cell linesElliott D SoRelle0https://orcid.org/0000-0002-3362-1028Joanne Dai1https://orcid.org/0000-0002-9879-4704Emmanuela N Bonglack2Emma M Heckenberg3Jeffrey Y Zhou4Stephanie N Giamberardino5Jeffrey A Bailey6Simon G Gregory7Cliburn Chan8Micah A Luftig9https://orcid.org/0000-0002-2964-1907Department of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, United States; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, United StatesDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, United StatesDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, United States; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United StatesDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, United StatesDepartment of Medicine, University of Massachusetts Medical School, Worcester, United StatesDuke Molecular Physiology Institute and Department of Neurology, Duke University School of Medicine, Durham, United StatesDepartment of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, United StatesDuke Molecular Physiology Institute and Department of Neurology, Duke University School of Medicine, Durham, United StatesDepartment of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, United StatesDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, United StatesLymphoblastoid 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.https://elifesciences.org/articles/62586Epstein-Barr viruslymphoblastoid cell linesvirus infectionNFkappaBB-cell differentiationsystems modeling |
| spellingShingle | 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 Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host–pathogen dynamics in lymphoblastoid cell lines eLife Epstein-Barr virus lymphoblastoid cell lines virus infection NFkappaB B-cell differentiation systems modeling |
| title | Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host–pathogen dynamics in lymphoblastoid cell lines |
| title_full | Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host–pathogen dynamics in lymphoblastoid cell lines |
| title_fullStr | Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host–pathogen dynamics in lymphoblastoid cell lines |
| title_full_unstemmed | Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host–pathogen dynamics in lymphoblastoid cell lines |
| title_short | Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host–pathogen dynamics in lymphoblastoid cell lines |
| title_sort | single cell rna seq reveals transcriptomic heterogeneity mediated by host pathogen dynamics in lymphoblastoid cell lines |
| topic | Epstein-Barr virus lymphoblastoid cell lines virus infection NFkappaB B-cell differentiation systems modeling |
| url | https://elifesciences.org/articles/62586 |
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