Sirbu Olga, Agarwal Gunjan, Giuliani Alessandro, Selvarajoo Kumar
Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
Engineering Systems and Design (ESD), Singapore University of Technology and Design (SUTD), Singapore, Republic of Singapore.
NPJ Syst Biol Appl. 2025 Aug 11;11(1):91. doi: 10.1038/s41540-025-00575-1.
Cancer cell populations, such as chronic lymphocytic leukemia (CLL), are characterized by aberrant proliferation and plasticity: cells may switch between states so increasing population heterogeneity. Previous works have shown that gene expression noise can impact cell-state transition. To gain better insights into transcriptome-wide expression dynamics and the effect of noise on state transition, here we investigate RNA-Seq data of proliferative (PC) and non-proliferative (NPC) CLL cells. Various data analytics were applied to the whole transcriptome, switch-like toggle (ON/OFF) genes, temporal differentially expressed (DE) genes, and randomly selected genes. Collectively, we identified 2713 temporal DE genes (DESeq2 with 4-fold, p < 0.05) and 1704 toggle genes shaping the differentiation process over a period of 96 h, with 604 overlapping genes between them. Despite their lower numbers compared to DE, toggle genes contributed significantly to gene expression noise in both cell types. Toggle gene analyses revealed the enrichment of genes involved in processes such as G-alpha signaling and muscle contraction as proliferation related RHO-GTPase, interleukin and chemokine signaling, and lymphoid cell communication. Thus, toggle genes, although being random ON/OFF genes, show gene expression functional variability. These results suggest that toggle genes play an important role in shaping cell population plasticity.
癌细胞群体，如慢性淋巴细胞白血病（CLL），具有异常增殖和可塑性的特征：细胞可能在不同状态之间转换，从而增加群体异质性。先前的研究表明，基因表达噪声会影响细胞状态转换。为了更好地了解全转录组范围的表达动态以及噪声对状态转换的影响，我们在此研究增殖性（PC）和非增殖性（NPC）CLL细胞的RNA测序数据。对整个转录组、开关样切换（开/关）基因、时间差异表达（DE）基因和随机选择的基因应用了各种数据分析方法。我们总共鉴定出2713个时间DE基因（DESeq2分析，变化4倍，p < 0.05）和1704个在96小时内塑造分化过程的切换基因，其中有604个重叠基因。尽管与DE基因相比数量较少，但切换基因在两种细胞类型中对基因表达噪声都有显著贡献。切换基因分析揭示了参与诸如G-α信号传导和肌肉收缩等过程的基因富集，这些过程与增殖相关的RHO-GTPase、白细胞介素和趋化因子信号传导以及淋巴细胞通讯有关。因此，切换基因尽管是随机的开/关基因，但显示出基因表达功能的变异性。这些结果表明，切换基因在塑造细胞群体可塑性方面发挥着重要作用。
