Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host-pathogen dynamics in lymphoblastoid cell lines.
Single-cell RNA-seq reveals transcriptomic heterogeneity mediated by host-pathogen dynamics in lymphoblastoid cell lines.
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单细胞RNA-seq揭示了淋巴母细胞系中宿主-病原体动力学介导的转录组异质性。
DOI：
10.7554/elife.62586
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发表时间：
2021-01-27
期刊：
影响因子：
7.7
通讯作者：
Luftig MA
中科院分区：
文献类型：
--
作者：
SoRelle ED;Dai J;Bonglack EN;Heckenberg EM;Zhou JY;Giamberardino SN;Bailey JA;Gregory SG;Chan C;Luftig MA
淋巴母细胞样细胞系（LCL）是通过用EB病毒（EBV）转化原代B细胞而产生的，并且广泛用作病毒肿瘤学、免疫学和人类遗传学研究中的模型系统。在这项研究中，我们的特点是单细胞转录谱的五个LCL，并提出了一个简单的离散时间模拟，探讨随机性对LCL克隆进化的影响。单细胞RNA测序（scRNA-seq）揭示了LCL内和LCL之间在免疫球蛋白同种型方面的大量表型异质性;涉及存活、活化和分化的病毒调节宿主途径;病毒复制状态;和氧化应激。这种异质性可能归因于原代B细胞和宿主-病原体动力学的内在差异。随机模拟表明，初始原代细胞的异质性，随机采样，在文化中的时间，甚至轻微的差异表型特异性健身可以大大有助于动态多样性的名义上克隆细胞的群体。
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.