PDF(Pubmed)
Abstract：
Foreign body response (FBR) is a universal reaction to implanted biomaterial that can affect the function and longevity of the implant. A few studies have attempted to identify targets for treating FBR through the use of single-cell RNA sequencing (scRNA-seq), though the generalizability of these findings from an individual study may be limited. In our study, we perform a meta-analysis of scRNA-seq data from all available FBR mouse studies and integrate these data to identify gene signatures specific to FBR across different models and anatomic locations. We identify subclusters of fibroblasts and macrophages that emerge in response to foreign bodies and characterize their signaling pathways, gene ontology terms, and downstream mediators. The fibroblast subpopulations enriched in the setting of FBR demonstrated significant signaling interactions in the transforming growth factor-beta (TGF-β) signaling pathway, with known pro-fibrotic mediators identified as top expressed genes in these FBR-derived fibroblasts. In contrast, FBR-enriched macrophage subclusters highly expressed pro-fibrotic and pro-inflammatory mediators downstream of tumor necrosis factor (TNF) signaling. Cell-cell interactions were additionally interrogated using CellChat, with identification of key signaling interactions enriched between fibroblasts and macrophages in FBR. By combining multiple FBR datasets, our meta-analysis study identifies common cell-specific gene signatures enriched in foreign body reactions, providing potential therapeutic targets for patients requiring medical implants across a myriad of devices and indications.
摘要：
异物反应（FBR）是对植入的生物材料的普遍反应，可以影响植入物的功能和寿命。一些研究试图通过使用单细胞RNA测序（scRNA-seq）来确定治疗FBR的靶标。尽管这些研究结果的普遍性可能有限。在我们的研究中,我们对所有可用的FBR小鼠研究的scRNA-seq数据进行了荟萃分析,并整合了这些数据以鉴定FBR在不同模型和解剖位置的特异性基因特征.我们确定了响应异物而出现的成纤维细胞和巨噬细胞亚簇，并表征了它们的信号通路。基因本体论术语，和下游中介。富含FBR的成纤维细胞亚群在转化生长因子-β（TGF-β）信号通路中表现出显著的信号相互作用，已知的促纤维化介质被鉴定为这些FBR衍生的成纤维细胞中的最高表达基因。相比之下,富含FBR的巨噬细胞亚簇高度表达肿瘤坏死因子（TNF）信号下游的促纤维化和促炎介质。还使用CellChat询问了细胞间的相互作用，鉴定FBR中成纤维细胞和巨噬细胞之间富集的关键信号传导相互作用。通过组合多个FBR数据集，我们的荟萃分析研究确定了富含异物反应的常见细胞特异性基因特征，在无数的设备和适应症中，为需要医疗植入物的患者提供潜在的治疗目标。
