Single‐cell sequencing combined with spatial transcriptomics reveals that the IRF7 gene in M1 macrophages inhibits the occurrence of pancreatic cancer by regulating lipid metabolism‐related mechanisms

作者：Ting Zhan, Yanli Zou, Zheng Han, Xiao-Rong Tian, Xiao-Rong Tian, Mengge Chen, Jiaxi Liu, Xiulin Yang, Qingxi Zhu, Meng Liu, Wei Chen, Mingtao Chen, Xiaodong Huang, Jie Tan, Weijie Liu, Xia Tian, Xia Tian · 发表于：Clinical and Translational Medicine · 年份：2024 · DOI：10.1002/ctm2.1799 · 被引用次数：21 · 研究领域：Extracellular vesicles in disease、Single-cell and spatial transcriptomics、Immune cells in cancer

AIM: The main focus of this study is to explore the molecular mechanism of IRF7 regulation on RPS18 transcription in M1-type macrophages in pancreatic adenocarcinoma (PAAD) tissue, as well as the transfer of RPS18 by IRF7 via exosomes to PAAD cells and the regulation of ILF3 expression. METHODS: By utilising single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics (ST) data from the Gene Expression Omnibus database, we identified distinct cell types with significant expression differences in PAAD tissue. Among these cell types, we identified those closely associated with lipid metabolism. The differentially expressed genes within these cell types were analysed, and target genes relevant to prognosis were identified. Flow cytometry was employed to assess the expression levels of target genes in M1 and M2 macrophages. Cell lines with target gene knockout were constructed using CRISPR/Cas9 editing technology, and cell lines with target gene knockdown and overexpression were established using lentiviral vectors. Additionally, a co-culture model of exosomes derived from M1 macrophages with PAAD cells was developed. The impact of M1 macrophage-derived exosomes on the lipid metabolism of PAAD cells in the model was evaluated through metabolomics analysis. The effects of M1 macrophage-derived exosomes on the viability, proliferation, division, migration and apoptosis of PAAD cells were assessed using MTT assay, flow cytometry, EdU assay, wound healing assay, Transwell ...