Natural killer (NK) cells are essential in controlling cancer and infection. However, little is known about the dynamics of the transcriptional regulatory machinery during NK cell differentiation. In this study, we applied the assay of transposase accessible chromatin with sequencing (ATAC-seq) technique in a home-developed in vitro NK cell differentiation system. Analysis of ATAC-seq data illustrated two distinct transcription factor (TF) clusters that dynamically regulate NK cell differentiation. Moreover, two TFs from the second cluster, FOS-like 2 (FOSL2) and early growth response 2 (EGR2), were identified as novel essential TFs that control NK cell maturation and function. Knocking down either of these two TFs significantly impacted NK cell differentiation. Finally, we constructed a genome-wide transcriptional regulatory network that provides a better understanding of the regulatory dynamics during NK cell differentiation.
天然杀伤（NK）细胞是先天性淋巴细胞，可保护宿主免受感染或癌细胞侵袭。此外，基于NK细胞的免疫疗法已成为癌症治疗中的新兴力量，并将在未来疾病治疗中发挥重要作用，而NK细胞用于免疫治疗依赖于大量具有最佳细胞活性的NK细胞。因此，全面了解NK细胞的分化过程对于提高临床治疗的有效性尤其重要。在这项研究中，我们利用ATAC-seq技术在体外诱导NK细胞分化系统中检测NK细胞分化过程中染色质可及性的变化。对ATAC-seq数据的分析发现两个不同的转录因子（TF）簇动态调控NK细胞的分化。 此外，来自第二个簇的两个TFs ，FOSL2和EGR2，被确定为调控NK细胞成熟和功能的新的必需转录因子。 敲低这两个TF中的任何一个，都会明显影响NK细胞的分化。 最后，我们构建了一个全基因组范围的转录调控网络，可以全面了解NK细胞的分化过程。





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