Natural killer (NK) cell lines, including YTS, NK92, NK3.3, and NKL, represent excellent models for the study of human natural killer cells. While phenotypic and functional differences between these cell lines have been reported, a multi-parametric study, encompassing genomic, phenotypic, and functional assays, has not been performed. Here, using a combination of techniques including microarray and copy number analyses, flow cytometry, and functional assays, we provide in-depth genetic, functional, and phenotypic comparison of YTS, NK92, NK3.3, and NKL cell lines. Specifically, we found that while the cell lines shared similarities in enrichment of growth and survival pathways, they had differential expression of 557 genes, including genes related to NK cell development, survival, and function. In addition, we provide genetic and phenotypic analyses that demonstrate distinct developmental origins of NK92, YTS, and NKL cell lines. Specifically, NK92 has a phenotype associated with the CD56bright NK cell subset, while both YTS and NKL appear more CD56dim-like. Finally, by classifying cell lines based on their lytic potential, we identified genes differentially expressed between NK cell lines with high and low lytic function. Taken together, these data provide the first comprehensive genetic, phenotypic, and functional analyses of these commonly used NK cell lines and provides deeper understanding into their origins and function. This will ultimately improve their use as models for human NK cell biology.

中文翻译：

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人类 NK 细胞系的全基因组分析和功能分析。


自然杀伤 (NK) 细胞系，包括 YTS、NK92、NK3.3 和 NKL，代表了人类自然杀伤细胞研究的优秀模型。虽然这些细胞系之间的表型和功能差异已被报道，但尚未进行涵盖基因组、表型和功能测定的多参数研究。在这里，我们结合使用微阵列和拷贝数分析、流式细胞术和功能测定等技术，对 YTS、NK92、NK3.3 和 NKL 细胞系进行深入的遗传、功能和表型比较。具体来说，我们发现虽然这些细胞系在生长和生存途径富集方面具有相似性，但它们具有 557 个基因的差异表达，包括与 NK 细胞发育、生存和功能相关的基因。此外，我们还提供遗传和表型分析，证明 NK92、YTS 和 NKL 细胞系的不同发育起源。具体来说，NK92 具有与 CD56bright NK 细胞亚群相关的表型，而 YTS 和 NKL 看起来更像 CD56dim。最后，通过根据细胞裂解潜力对细胞系进行分类，我们鉴定了具有高裂解功能和低裂解功能的 NK 细胞系之间差异表达的基因。总而言之，这些数据首次对这些常用 NK 细胞系进行了全面的遗传、表型和功能分析，并提供了对其起源和功能的更深入了解。这最终将改善它们作为人类 NK 细胞生物学模型的用途。