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Updated: Nov 19, 2025
10:23
Single-cell Gene Expression Using Multiplex RT-qPCR to Characterize Heterogeneity of Rare Lymphoid Populations
Published on: January 19, 2017
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Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host-pathogen dynamics in lymphoblastoid cell
Elliott D SoRelle1,2, Joanne Dai1, Emmanuela N Bonglack1,3
1Department of Molecular Genetics and Microbiology, Center for Virology, Duke University School of Medicine, Durham, United States.
Elife
|January 27, 2021
Summary
Lymphoblastoid cell lines (LCLs) exhibit significant cell diversity due to Epstein-Barr virus (EBV) infection. This study reveals that initial cell variations and random processes drive LCL clonal evolution and heterogeneity.
Area of Science:
- Immunology
- Virology
- Genetics
- Cell Biology
Background:
- Lymphoblastoid cell lines (LCLs) are crucial models for studying B cell biology, viral oncology, immunology, and human genetics.
- These cell lines are generated by Epstein-Barr virus (EBV) transformation of primary B cells.
- Understanding LCL heterogeneity is key to interpreting research findings.
Purpose of the Study:
- To characterize the single-cell transcriptomic profiles of LCLs.
- To explore the influence of stochasticity on LCL clonal evolution using discrete-time simulations.
- To identify sources of phenotypic heterogeneity within LCL populations.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) was employed to analyze five LCLs.
- Discrete-time simulations were developed to model LCL clonal evolution.
- Phenotypic heterogeneity was assessed across multiple cellular characteristics.
Main Results:
- scRNA-seq revealed substantial phenotypic heterogeneity within and across LCLs.
- Heterogeneity was observed in immunoglobulin isotype, EBV-modulated host pathways (survival, activation, differentiation), viral replication state, and oxidative stress.
- Simulations indicated that initial primary cell heterogeneity, random sampling, culture time, and fitness differences contribute to diversity in nominally clonal populations.
Conclusions:
- Phenotypic heterogeneity in LCLs is driven by intrinsic primary B cell variations and host-pathogen dynamics.
- Stochastic processes significantly contribute to the observed diversity in LCL populations over time.
- These findings highlight the importance of considering cellular heterogeneity in LCL research.
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