ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1611114
This article is part of the Research TopicBiomarkers and Beyond: Predicting Course and Tailoring Treatment in Inflammatory Bowel DiseasesView all 16 articles
Impact of Hypercoagulable State on Crohn's Disease Severity and Progression: Transcriptomic and Single-Cell Analyses of the Ileum
Provisionally accepted
- 1Nanfang Hospital, Southern Medical University, Guangzhou, China
- 2The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, China
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ABSTRACT Background: The mechanisms linking hypercoagulability to disease severity in Crohn's disease (CD) remain poorly understood. Through integrated transcriptomic and single-cell analyses of ileal tissues, we identified a novel CCR6+OLFM4+ intestinal stem cell subpopulation that bridges coagulation and inflammation in CD. Methods: A cohort of 78 CD patients was established, utilizing transcriptomic data from three independent ileal samples obtained from the GEO database as discovery and validation datasets. Coagulation-related DEGs (CRGs) were determined via AmiGO 2 and KEGG databases. Based on these CRGs, CD patients were subclustered, coagulation scores were calculated, and gene expression changes were evaluated. Public single-cell RNA sequencing data from CD patient ileal epithelial cells were analyzed to identify key target cells influenced by coagulation. Immune infiltration was evaluated based on coagulation scores across subgroups. Ileal tissues from CD patients with different coagulation statuses were examined using Immunofluorescence Staining. Results: Single-cell analysis of ileal epithelium revealed a novel CCR6+OLFM4+ stem cell subpopulation that was significantly expanded in CD patients with hypercoagulability (P<0.05). These cells showed marked upregulation of PI3K-Akt signaling and correlated strongly with disease severity. Immunofluorescence validation confirmed a 2.3-fold increase in CCR6+OLFM4+ cells in the epithelial layer of hypercoagulable CD patients compared to normocoagulable controls. The concurrent activation of coagulation pathways and immune cell infiltration in CD ileum suggests this stem cell subpopulation may serve as a critical link between hypercoagulability and disease progression. Conclusion: Our findings nominate CCR6+OLFM4+ stem cells as cellular mediators
Keywords: Coagulability, IBD - inflammatory bowel disease, Crohn desease, biomarker, bioinformatics
Received: 13 Apr 2025; Accepted: 27 Aug 2025.
Copyright: © 2025 Wu, Wu, Yang, Xie, Xie, Bai, Huang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Miaoxing Huang, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong, China
Side Liu, Nanfang Hospital, Southern Medical University, Guangzhou, China
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