KTH Royal Institute of Technology, School of Chemistry, Biotechnology and Health, Science for Life Laboratory, Tomtebodavägen 23A, 171 65 Stockholm, Sweden.
Cardiovascular Medicine Unit, Center for Molecular Medicine, Department of Medicine Solna, Karolinska Institutet, Stockholm, Karolinska University Hospital, Solna, Sweden.
Cell Immunol. 2020 Sep;355:104148. doi: 10.1016/j.cellimm.2020.104148. Epub 2020 Jun 12.
Macrophages are highly plastic immune cells with temporally distinct transcriptome changes upon lipopolysaccride (LPS) activation. However, to what extent transcriptome reprogramming is mediated via spatial chromatin looping is not well studied. We generated high resolution chromatin interaction maps for LPS-stimulated THP-1 macrophages (0 and 2 h) using capture Hi-C. Success of LPS stimulation was validated with transcriptome sequencing. Circa 2900 genes changed their interaction profile upon LPS stimulation and those gaining interactions were enriched for LPS response relevant processes, suggesting a substantial role for distal regulation. Immune and cardiovascular risk variants were enriched within the interacting regions, thereby providing insights into macrophage biology.
巨噬细胞是高度可塑性的免疫细胞，在脂多糖 (LPS) 激活时具有暂时不同的转录组变化。然而，转录组重编程在多大程度上是通过空间染色质环介导的，目前研究还不够充分。我们使用捕获 Hi-C 技术为 LPS 刺激的 THP-1 巨噬细胞（0 和 2 小时）生成了高分辨率的染色质相互作用图谱。使用转录组测序验证了 LPS 刺激的成功。大约 2900 个基因在 LPS 刺激后改变了它们的相互作用谱，那些获得相互作用的基因富集了与 LPS 反应相关的过程，这表明远端调控具有重要作用。免疫和心血管风险变异在相互作用区域内富集，从而为巨噬细胞生物学提供了新的见解。
