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

Publication ,  Journal Article
SoRelle, ED; Dai, J; Bonglack, EN; Heckenberg, EM; Zhou, JY; Giamberardino, SN; Bailey, JA; Gregory, SG; Chan, C; Luftig, MA
Published in: Elife
January 27, 2021

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.

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Published In

Elife

DOI

EISSN

2050-084X

Publication Date

January 27, 2021

Volume

10

Location

England

Related Subject Headings

  • Transcriptome
  • Single-Cell Analysis
  • RNA-Seq
  • Humans
  • Host-Pathogen Interactions
  • Herpesvirus 4, Human
  • Cell Line
  • B-Lymphocytes
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
 

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SoRelle, E. D., Dai, J., Bonglack, E. N., Heckenberg, E. M., Zhou, J. Y., Giamberardino, S. N., … Luftig, M. A. (2021). Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host-pathogen dynamics in lymphoblastoid cell lines. Elife, 10. https://doi.org/10.7554/eLife.62586
SoRelle, Elliott D., Joanne Dai, Emmanuela N. Bonglack, Emma M. Heckenberg, Jeffrey Y. Zhou, Stephanie N. Giamberardino, Jeffrey A. Bailey, Simon G. Gregory, Cliburn Chan, and Micah A. Luftig. “Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host-pathogen dynamics in lymphoblastoid cell lines.Elife 10 (January 27, 2021). https://doi.org/10.7554/eLife.62586.
SoRelle ED, Dai J, Bonglack EN, Heckenberg EM, Zhou JY, Giamberardino SN, et al. Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host-pathogen dynamics in lymphoblastoid cell lines. Elife. 2021 Jan 27;10.
SoRelle, Elliott D., et al. “Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host-pathogen dynamics in lymphoblastoid cell lines.Elife, vol. 10, Jan. 2021. Pubmed, doi:10.7554/eLife.62586.
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.

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

January 27, 2021

Volume

10

Location

England

Related Subject Headings

  • Transcriptome
  • Single-Cell Analysis
  • RNA-Seq
  • Humans
  • Host-Pathogen Interactions
  • Herpesvirus 4, Human
  • Cell Line
  • B-Lymphocytes
  • 42 Health sciences
  • 32 Biomedical and clinical sciences