Todorov Helena, Prieux Margaux, Laubreton Daphne, Bouvier Matteo, Wang Shaoying, de Bernard Simon, Arpin Christophe, Cannoodt Robrecht, Saelens Wouter, Bonnaffoux Arnaud, Gandrillon Olivier, Crauste Fabien, Saeys Yvan, Marvel Jacqueline
Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium.
iScience. 2022 Aug 13;25(9):104927. doi: 10.1016/j.isci.2022.104927. eCollection 2022 Sep 16.
In this work, we studied the generation of memory precursor cells following an acute infection by analyzing single-cell RNA-seq data that contained CD8 T cells collected during the postinfection expansion phase. We used different tools to reconstruct the developmental trajectory that CD8 T cells followed after activation. Cells that exhibited a memory precursor signature were identified and positioned on this trajectory. We found that these memory precursors are generated continuously with increasing numbers arising over time. Similarly, expression of genes associated with effector functions was also found to be raised in memory precursors at later time points. The ability of cells to enter quiescence and differentiate into memory cells was confirmed by BrdU pulse-chase experiment . Analysis of cell counts indicates that the vast majority of memory cells are generated at later time points from cells that have extensively divided.
在这项研究中,我们通过分析单细胞RNA测序数据来研究急性感染后记忆前体细胞的产生,这些数据包含感染后扩增阶段收集的CD8 T细胞。我们使用不同的工具来重建CD8 T细胞激活后所遵循的发育轨迹。鉴定出表现出记忆前体特征的细胞,并将其定位在该轨迹上。我们发现这些记忆前体是持续产生的,随着时间的推移数量不断增加。同样,在后期时间点,记忆前体中与效应功能相关的基因表达也被发现有所升高。通过BrdU脉冲追踪实验证实了细胞进入静止状态并分化为记忆细胞的能力。细胞计数分析表明,绝大多数记忆细胞是在后期时间点由已经广泛分裂的细胞产生的。