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bioRxiv · 10.1101/2020.09.24.311886

Single-cell characterization of transcriptomic heterogeneity in lymphoblastoid cell lines

Sorelle, E. D.·Dai, J.·Zhou, J. Y.·Giamberardino, S.·Bailey, J. A.·Gregory, S.·Chan, C.·Luftig, M. A.
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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 revealed substantial phenotypic heterogeneity within and across LCLs with respect to immunoglobulin isotype; virus-modulated host pathways involved in survival, proliferation, 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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Sorelle, E. D., Dai, J., Zhou, J. Y., Giamberardino, S., Bailey, J. A., Gregory, S., Chan, C., Luftig, M. A.. 2020-09-25. Single-cell characterization of transcriptomic heterogeneity in lymphoblastoid cell lines. https://doi.org/10.1101/2020.09.24.311886

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