麻省理工学院和哈佛大学的布罗德研究所Ramnik J. Xavier小组宣布他们的最新研究探明了狭窄性克罗恩病的单细胞和空间转录组学强调了纤维化相关网络。2025年6月25日出版的《自然—遗传学》发表了这项成果。

由于缺乏机制表征和治疗方案，该团队对来自21名CD患者和10名非炎症性肠病（IBD）患者的61个样本进行了单细胞和空间转录组学配对。肠道狭窄的特征是免疫细胞增加，包括IgG⁺浆细胞、CCR7-hi CD4⁺ T细胞和炎性成纤维细胞。空间转录组学表明，关键亚群在病变组织中共定位，并确定了Cajal和肠神经元间质细胞等其他群体。

此外，该研究团队将基因表达映射到肠道生物地理上，发现已知的遗传风险位点富集在离散的空间模块中，由炎性成纤维细胞和淋巴滤泡的存在所定义。总的来说，他们的数据集绘制了限制CD的关键转录组和细胞网络，并突出了多细胞遗传风险因素的空间组织。

据介绍，纤维化是克罗恩病（CD）的主要并发症，其特征是细胞外基质过度沉积，导致狭窄和功能损害。

附：英文原文

Title: Single-cell and spatial transcriptomics of stricturing Crohn’s disease highlights a fibrosis-associated network

Author: Kong, Lingjia, Subramanian, Sathish, Segerstolpe, sa, Tran, Vy, Shih, Angela R., Carter, Grace T., Kunitake, Hiroko, Twardus, Shaina W., Li, Jasmine, Gandhi, Shivam, Kaper, Marco E., Cauley, Christy, Chen, Eric J., Porter, Caroline B. M., Delorey, Toni M., Bordeianou, Liliana, Ricciardi, Rocco, Ananthakrishnan, Ashwin N., Lau, Helena, Graham, Daniel B., Hodin, Richard, Deguine, Jacques, Smillie, Christopher S., Xavier, Ramnik J.

Issue&Volume: 2025-06-25

Abstract: Fibrosis is a major complication of Crohn’s disease (CD) marked by excess deposition of extracellular matrix, leading to stricturing and functional impairment. As mechanistic characterization and therapeutic options are lacking, we paired single-cell and spatial transcriptomics in 61 samples from 21 patients with CD and 10 patients without inflammatory bowel disease (IBD). Intestinal strictures were characterized by increased immune cells, including IgG+ plasma cells, CCR7-hi CD4+ T cells and inflammatory fibroblasts. Spatial transcriptomics showed that key subsets colocalize within diseased tissues and identified additional populations such as interstitial cells of Cajal and enteric neurons. Furthermore, we mapped gene expression onto intestinal biogeography, finding that known genetic risk loci are enriched within discrete spatial modules, defined by the presence of inflammatory fibroblasts and lymphoid follicles. Altogether, our datasets chart the key transcriptomic and cellular networks in stricturing CD and highlight the spatial organization of multicellular genetic risk factors.

DOI: 10.1038/s41588-025-02225-y

Source: https://www.nature.com/articles/s41588-025-02225-y