Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230021, China.
Department of Oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230021, China; CAS Center for Excellence in Molecular Cell Sciences, The CAS Key Laboratory of Innate Immunity and Chronic Disease, University of Science and Technology of China, Hefei 230027, China.
Genomics Proteomics Bioinformatics. 2020 Oct;18(5):501-515. doi: 10.1016/j.gpb.2020.12.003. Epub 2020 Dec 30.
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.
自然杀伤 (NK) 细胞在控制癌症和感染方面至关重要。然而，人们对 NK 细胞分化过程中转录调控机制的动态变化知之甚少。在这项研究中，我们在自主开发的体外 NK 细胞分化系统中应用了转座酶可及染色质测序 (ATAC-seq) 技术。ATAC-seq 数据分析表明，有两个不同的转录因子 (TF) 簇可以动态调控 NK 细胞分化。此外，第二个 TF 簇中的两个 TF，即 FOS 样 2 (FOSL2) 和早期生长反应 2 (EGR2)，被鉴定为控制 NK 细胞成熟和功能的新型必需 TF。敲除这两个 TF 中的任何一个都会显著影响 NK 细胞的分化。最后，我们构建了一个全基因组转录调控网络，有助于更好地理解 NK 细胞分化过程中的调控动态。
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