Kim Yoon-Seob, Shin Sun, Choi Eun Ji, Moon Seong Won, Jung Chan Kwon, Chung Yeun-Jun, Lee Sug Hyung
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Precision Medicine Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; IRCGP, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
J Invest Dermatol. 2022 Dec;142(12):3232-3242.e16. doi: 10.1016/j.jid.2022.06.014. Epub 2022 Jul 16.
Although macrophage‒epithelioid cell (EPC)‒giant cell (GC) differentiation is acknowledged in foreign body reaction (FBR), the exact molecular features remain elusive. To discover the molecular profiles of EPC and GC, we analyzed mouse sponge and silk FBRs by integrating single-cell RNA sequencing and spatial sequencing, which identified seven cell types, including macrophages and fibroblasts. Macrophages comprised three subsets with a trajectory from M2-like cell to EPC to GC. They were different in many aspects, including cytokine, extracellular matrix organization/degradation, epithelial modules, and glycolysis that were consistent in both sponge and silk FBRs. EPCs exhibited epithelial modules and extracellular matrix organization, and GCs showed glycolysis, extracellular matrix degradation, and cell fusion signatures. Cellular interactions in GCs and M2-like cells were predicted to be higher than that in EPCs. High expression of inflammation or fusion-related (GPNMB, matrix metalloproteinase 12 gene MMP12, DCSTAMP) and glycolysis-related (PGAM1, ALDOA) genes was identified in GCs of human/mouse tissues, suggesting them as GC-specific markers. Our study identified unique signatures of EPCs and GCs in FBR. Importantly, GCs showed strong glycolysis signatures and cellular interactions, suggesting their activation in FBR. Our data on EPC and GC refinement and GC-specific markers enable the understanding of FBR and help to explore preventive and therapeutic management strategies for skin FBRs.
尽管在异物反应（FBR）中巨噬细胞-上皮样细胞（EPC）-巨细胞（GC）分化已得到公认，但其确切的分子特征仍不清楚。为了发现EPC和GC的分子特征，我们通过整合单细胞RNA测序和空间测序分析了小鼠海绵和丝线FBR，确定了七种细胞类型，包括巨噬细胞和成纤维细胞。巨噬细胞包括三个亚群，具有从M2样细胞到EPC再到GC的轨迹。它们在许多方面存在差异，包括细胞因子、细胞外基质组织/降解、上皮模块和糖酵解，这些在海绵和丝线FBR中都是一致的。EPC表现出上皮模块和细胞外基质组织，而GC表现出糖酵解、细胞外基质降解和细胞融合特征。预测GC和M2样细胞中的细胞相互作用高于EPC中的。在人/小鼠组织的GC中鉴定出炎症或融合相关（GPNMB、基质金属蛋白酶12基因MMP12、DCSTAMP）和糖酵解相关（PGAM1、ALDOA）基因的高表达，表明它们是GC特异性标志物。我们的研究确定了FBR中EPC和GC的独特特征。重要的是，GC表现出强烈的糖酵解特征和细胞相互作用，表明它们在FBR中被激活。我们关于EPC和GC细化以及GC特异性标志物的数据有助于理解FBR，并有助于探索皮肤FBR的预防和治疗管理策略。
