Lin WG, Huang SY, Lan H, Zheng XX, Liu XB, Xu ZG, Ke MH. Spatiotemporal atlas of internal hemorrhoids in rats elucidated using integrated single-cell RNA sequencing and spatial transcriptomics. World J Gastroenterol 2026; 32(41): 121893 [DOI: 10.3748/wjg.121893]
Corresponding Author of This Article
Min-Hui Ke, PhD, Chief Physician, Full Professor, Department of Proctology, The Second People’s Hospital Affiliated with Fujian University of Traditional Chinese Medicine, No. 282 Wusi Road, Gulou District, Fuzhou 350003, Fujian Province, China. 48330132@qq.com
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Gastroenterology & Hepatology
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research-article
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Lin WG, Huang SY, Lan H, Zheng XX, Liu XB, Xu ZG, Ke MH. Spatiotemporal atlas of internal hemorrhoids in rats elucidated using integrated single-cell RNA sequencing and spatial transcriptomics. World J Gastroenterol 2026; 32(41): 121893 [DOI: 10.3748/wjg.121893]
World J Gastroenterol. Nov 7, 2026; 32(41): 121893 Published online Nov 7, 2026. doi: 10.3748/wjg.121893
Spatiotemporal atlas of internal hemorrhoids in rats elucidated using integrated single-cell RNA sequencing and spatial transcriptomics
Wei-Gan Lin, Shu-Yan Huang, Hong Lan, Xia-Xia Zheng, Xian-Bao Liu, Zhen-Guo Xu, Min-Hui Ke
Wei-Gan Lin, Shu-Yan Huang, Hong Lan, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian Province, China
Xia-Xia Zheng, Xian-Bao Liu, Min-Hui Ke, Department of Proctology, The Second People’s Hospital Affiliated with Fujian University of Traditional Chinese Medicine, Fuzhou 350003, Fujian Province, China
Zhen-Guo Xu, Department of Pathology, The Second People’s Hospital Affiliated with Fujian University of Traditional Chinese Medicine, Fuzhou 350003, Fujian Province, China
Author contributions: Lin WG contributed to experimental design, manuscript writing, image collection and transcriptomic analysis; Huang SY and Lan H were responsible for animal modeling; Zheng XX, Liu XB, and Xu ZG conducted pathology analysis; Ke MH provided research guidance, manuscript review and obtained funding; and all authors thoroughly reviewed and endorsed the final manuscript.
AI contribution statement: AI tools were used solely for linguistic refinement and formatting assistance. No AI tool was involved in the generation of research data or interpretation of results. All AI-generated outputs were critically reviewed and revised by the authors.
Supported by the General Program of the National Natural Science Foundation of China, No. 81774118; and the Medical Innovation Project of Fujian Provincial Health Commission, No. 2024CXB013.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Fujian Academy of Traditional Chinese Medicine, approval No. FJACMS-PZ-20250016.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All experimental data of this study will be shared upon reasonable request.
Corresponding author: Min-Hui Ke, PhD, Chief Physician, Full Professor, Department of Proctology, The Second People’s Hospital Affiliated with Fujian University of Traditional Chinese Medicine, No. 282 Wusi Road, Gulou District, Fuzhou 350003, Fujian Province, China. 48330132@qq.com
Received: April 7, 2026 Revised: May 11, 2026 Accepted: June 9, 2026 Published online: November 7, 2026 Processing time: 164 Days and 6.4 Hours
Abstract
BACKGROUND
Internal hemorrhoids are a highly prevalent vascular anorectal disease worldwide. However, the pathological mechanisms of disease progression, and particularly early-stage cellular heterogeneity, intercellular communication, and microenvironmental dynamics, remain poorly defined.
AIM
To investigate the spatiotemporal transcriptome profile of internal hemorrhoids development in rats.
METHODS
We established a rat model of internal hemorrhoids and performed integrated single-cell RNA sequencing, spatial transcriptomic, histopathology, and western blot analyses to elucidate the spatiotemporal mechanisms of hemorrhoid pathogenesis.
RESULTS
Macrophages switched from a proinflammatory phenotype to a reparative phenotype; fibroblasts mainly differentiated into growth factor-regulated subsets and profibrotic protomyofibroblasts; and vascular endothelial/smooth muscle cells participated in hemorrhoidal vascular remodeling. Spatial transcriptomic clarified the in situ distribution of key genes and spatiotemporal correlations between immune cell infiltration and extracellular matrix remodeling in early lesions. Multiomics revealed that Cd74+ macrophages act as early inflammatory switches, driving Igfbp5+ fibroblasts/protomyofibroblasts activation via Col-integrin interactions to trigger the phosphatidylinositol 3-kinase/protein kinase B signaling, synergistically promoting vascular dilation, inflammation, and fibrosis.
CONCLUSION
This study delineates a spatiotemporal transcriptomic landscape of internal hemorrhoid development in rats, revealing a pathogenic cascade from vascular inflammation to extracellular matrix remodeling.
Core Tip: This study integrates single-cell and spatial transcriptomics to reveal spatiotemporal dynamics in rat internal hemorrhoids. Macrophages shift from pro-inflammatory to pro-reparative phenotypes, while fibroblasts differentiate into growth factor-regulated and profibrotic subsets, driving vascular remodeling. Cd74⁺ macrophages act as early inflammatory switches, activating Igfbp5⁺ fibroblasts/protomyofibroblasts via collagen–integrin interactions and the phosphatidylinositol 3-kinase/protein kinase B signaling, thus promoting vascular dilation, inflammation, and fibrosis. These findings provide novel insights into hemorrhoid progression from inflammation to extracellular matrix remodeling.
