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
Materias:	Epstein-Barr virus lymphoblastoid cell lines virus infection NFkappaB B-cell differentiation systems modeling Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b49ae641f8704cfbb9d4caceb9a13345
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spelling	oai:doaj.org-article:b49ae641f8704cfbb9d4caceb9a133452021-11-11T14:28:55ZSingle-cell RNA-seq reveals transcriptomic heterogeneity mediated by host–pathogen dynamics in lymphoblastoid cell lines10.7554/eLife.625862050-084Xe62586https://doaj.org/article/b49ae641f8704cfbb9d4caceb9a133452021-01-01T00:00:00Zhttps://elifesciences.org/articles/62586https://doaj.org/toc/2050-084XLymphoblastoid 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.Elliott D SoRelleJoanne DaiEmmanuela N BonglackEmma M HeckenbergJeffrey Y ZhouStephanie N GiamberardinoJeffrey A BaileySimon G GregoryCliburn ChanMicah A LuftigeLife Sciences Publications LtdarticleEpstein-Barr viruslymphoblastoid cell linesvirus infectionNFkappaBB-cell differentiationsystems modelingMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Epstein-Barr virus lymphoblastoid cell lines virus infection NFkappaB B-cell differentiation systems modeling Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	Epstein-Barr virus lymphoblastoid cell lines virus infection NFkappaB B-cell differentiation systems modeling Medicine R Science Q Biology (General) QH301-705.5 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
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.
format	article
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
title	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_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_sort	single-cell rna-seq reveals transcriptomic heterogeneity mediated by host–pathogen dynamics in lymphoblastoid cell lines
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/b49ae641f8704cfbb9d4caceb9a13345
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Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host–pathogen dynamics in lymphoblastoid cell lines

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