英国威康桑格研究所Sarah A. Teichmann团队近期取得重要工作进展，他们通过将单细胞数据整合揭示了炎症性肠道疾病的化生现象。相关研究成果2024年11月20日在线发表于《自然》杂志上。

据介绍，胃肠道是一个多器官系统，对有效的营养吸收和屏障免疫至关重要。基因组学的进步和胃肠道疾病的激增推动了人们对健康和疾病中构成胃肠道组织的细胞进行分类的工作进展。

研究人员展示了25个单细胞RNA测序数据集的系统整合，这些数据集涵盖了发育和成年期整个健康胃肠道。研究人员使用新开发的自动质量控制方法（scAutoQC）对来自189个健康对照的385个样本进行了统一处理，从而得到了一个包含约110万个细胞和136个精细细胞状态的健康参考图谱。研究人员将涵盖胃肠道癌症、乳糜泻、溃疡性结肠炎和克罗恩病的12个胃肠道疾病数据集作为参考依据。

利用这160万个细胞资源（gutcellatlas.org），研究人员发现上皮细胞化生起源于肠道炎症性疾病中的干细胞，与幽门腺和布鲁纳腺中的细胞具有转录相似性。尽管以前与粘膜愈合有关，但研究人员现在通过招募包括T细胞和中性粒细胞在内的免疫细胞，将幽门腺化生细胞与炎症联系起来。

总之，研究人员描述了炎症诱导的干细胞变化，这些变化改变了粘膜组织结构并促进了进一步的炎症，这一概念适用于其他组织和疾病。

附：英文原文

Title: Single-cell integration reveals metaplasia in inflammatory gut diseases

Author: Oliver, Amanda J., Huang, Ni, Bartolome-Casado, Raquel, Li, Ruoyan, Koplev, Simon, Nilsen, Hogne R., Moy, Madelyn, Cakir, Batuhan, Polanski, Krzysztof, Gudio, Victoria, Meln-Ardanaz, Elisa, Sumanaweera, Dinithi, Dimitrov, Daniel, Milchsack, Lisa Marie, FitzPatrick, Michael E. B., Provine, Nicholas M., Boccacino, Jacqueline M., Dann, Emma, Predeus, Alexander V., To, Ken, Prete, Martin, Chapman, Jonathan A., Masi, Andrea C., Stephenson, Emily, Engelbert, Justin, Lobentanzer, Sebastian, Perera, Shani, Richardson, Laura, Kapuge, Rakeshlal, Wilbrey-Clark, Anna, Semprich, Claudia I., Ellams, Sophie, Tudor, Catherine, Joseph, Philomeena, Garrido-Trigo, Alba, Corraliza, Ana M., Oliver, Thomas R. W., Hook, C. Elizabeth, James, Kylie R., Mahbubani, Krishnaa T., Saeb-Parsy, Kourosh, Zilbauer, Matthias, Saez-Rodriguez, Julio, Hivik, Marte Lie, Bkkevold, Espen S., Stewart, Christopher J., Berrington, Janet E., Meyer, Kerstin B., Klenerman, Paul, Salas, Azucena, Haniffa, Muzlifah, Jahnsen, Frode L., Elmentaite, Rasa, Teichmann, Sarah A.

Issue&Volume: 2024-11-20

Abstract: The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics and a surge in gastrointestinal diseases1,2 has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease3. Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy gastrointestinal tract in development and in adulthood. We uniformly processed 385 samples from 189 healthy controls using a newly developed automated quality control approach (scAutoQC), leading to a healthy reference atlas with approximately 1.1 million cells and 136 fine-grained cell states. We anchor 12 gastrointestinal disease datasets spanning gastrointestinal cancers, coeliac disease, ulcerative colitis and Crohn’s disease to this reference. Utilizing this 1.6 million cell resource (gutcellatlas.org), we discover epithelial cell metaplasia originating from stem cells in intestinal inflammatory diseases with transcriptional similarity to cells found in pyloric and Brunner’s glands. Although previously linked to mucosal healing4, we now implicate pyloric gland metaplastic cells in inflammation through recruitment of immune cells including T cells and neutrophils. Overall, we describe inflammation-induced changes in stem cells that alter mucosal tissue architecture and promote further inflammation, a concept applicable to other tissues and diseases.

DOI: 10.1038/s41586-024-07571-1

Source: https://www.nature.com/articles/s41586-024-07571-1