Inflammatory bowel diseases (IBDs) are characterized by waves of relapse and remitting inflammation that lead to the remodeling of the cellular diversity of the gut. In Cell, Paolo Cadinu at al. chart the cellular and spatial structures of the colon in a mouse model of IBD. Using an image-based approach to spatial transcriptomics that can capture thousands of RNA molecules within single cells in their native tissue context, the authors find distinct populations of inflammation-associated fibroblasts (IAFs). The authors apply multiplexed-error robust-fluorescence in situ hybridization (MERFISH) in the colon of a dextran sodium sulfate (DSS)-induced mouse colitis model before treatment, early in disease, at peak inflammation, and after a DSS-free recovery period. They develop an anatomical-coordinate-free method to represent spatial structures and identify recurrent collection of cells, known as cellular neighborhoods, that capture DSS-induced spatial remodeling. At the recovery period, fibroblasts can maintain a memory of inflammatory insult for weeks. By analyzing receptor–ligand interactions, the authors find that IAFs have distinct roles in interactions with immune cells and other fibroblasts. Using a CXCL12-dependent fibroblast lineage tracing mouse, they show that the IAF populations arise from different healthy fibroblasts. Similar to mice, the analysis of data from individuals with ulcerative colitis shows that the IAFs and neighborhoods may contribute to the human disorder. This atlas provides a framework for the investigation of gut inflammation at the tissue level that could potentially be applied to other tissues.

Original reference: Cell 187, 2010–2028.e30 (2024)

炎症性肠病（IBD）的特点是反复发作和缓解炎症，导致肠道细胞多样性的重塑。在《细胞》中，保罗·卡迪努 (Paolo Cadinu) 等人。绘制 IBD 小鼠模型结肠的细胞和空间结构图。作者使用基于图像的空间转录组学方法，可以捕获其天然组织环境中单个细胞内的数千个 RNA 分子，发现了不同的炎症相关成纤维细胞 (IAF) 群体。作者在治疗前、疾病早期、炎症高峰期和无 DSS 恢复期后，在右旋糖酐硫酸钠 (DSS) 诱导的小鼠结肠炎模型的结肠中应用多重错误鲁棒荧光原位杂交 (MERFISH) 。他们开发了一种无解剖坐标的方法来表示空间结构并识别细胞的循环集合（称为细胞邻域），捕获 DSS 诱导的空间重塑。在恢复期，成纤维细胞可以将炎症损伤的记忆维持数周。通过分析受体-配体相互作用，作者发现 IAF 在与免疫细胞和其他成纤维细胞的相互作用中具有独特的作用。他们使用 CXCL12 依赖性成纤维细胞谱系追踪小鼠，表明 IAF 群体源自不同的健康成纤维细胞。与小鼠类似，对溃疡性结肠炎患者数据的分析表明，IAF 和邻近区域可能会导致人类疾病。该图谱为在组织水平上研究肠道炎症提供了一个框架，该框架可能适用于其他组织。

原始参考文献： Cell 187，2010–2028.e30 (2024)