Moffitt Cancer Center, Integrated Mathematical Oncology, USF Magnolia Drive, Tampa, FL 33612, USA.
Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, 4202 E Fowler Ave, Tampa, FL 33612, USA.
Cells. 2023 Jul 14;12(14):1849. doi: 10.3390/cells12141849.
Many cancer cell lines are aneuploid and heterogeneous, with multiple karyotypes co-existing within the same cell line. Karyotype heterogeneity has been shown to manifest phenotypically, thus affecting how cells respond to drugs or to minor differences in culture media. Knowing how to interpret karyotype heterogeneity phenotypically would give insights into cellular phenotypes before they unfold temporally. Here, we re-analyzed single cell RNA (scRNA) and scDNA sequencing data from eight stomach cancer cell lines by placing gene expression programs into a phenotypic context. Using live cell imaging, we quantified differences in the growth rate and contact inhibition between the eight cell lines and used these differences to prioritize the transcriptomic biomarkers of the growth rate and carrying capacity. Using these biomarkers, we found significant differences in the predicted growth rate or carrying capacity between multiple karyotypes detected within the same cell line. We used these predictions to simulate how the clonal composition of a cell line would change depending on density conditions during experiments. Once validated, these models can aid in the design of experiments that steer evolution with density-dependent selection.
许多癌细胞系是非整倍体且异质性的，同一细胞系中存在多种核型。核型异质性已被证明表型上表现出来，从而影响细胞对药物的反应或对培养基中微小差异的反应。了解如何表型上解释核型异质性，可以在时间上展开之前洞察细胞表型。在这里，我们通过将基因表达程序置于表型背景中，重新分析了来自八个胃癌细胞系的单细胞 RNA（scRNA）和 scDNA 测序数据。通过活细胞成像，我们量化了八个细胞系之间的生长速度和接触抑制的差异，并利用这些差异优先考虑了生长速度和承载能力的转录组生物标志物。使用这些生物标志物，我们发现同一细胞系内检测到的多个核型之间在预测的生长速度或承载能力上存在显著差异。我们使用这些预测来模拟细胞系的克隆组成如何根据实验期间的密度条件发生变化。一旦得到验证，这些模型可以帮助设计依赖密度选择的实验，从而引导进化。
