Single-cell transcriptomic profiling reveals fibroblast activation in hemorrhoids

Hemorrhoids, often regarded as the Achilles' heel of human evolution, have persistently plagued humanity due to modern lifestyle and work habits. Even surgical resection fails to offer a complete solution, underscoring the urgency of understanding their underlying mechanisms. To comprehensively elucidate the development of hemorrhoids and devise effective treatment strategies, we employed single-cell RNA sequencing to dissect the cellular heterogeneity and dynamic changes during hemorrhoid progression. We detected a total of 30,205 cells, categorizing them into 31 distinct clusters that encompass a diverse range of cell types. Notably, cell type compositions evolved significantly during hemorrhoid development. With the development of hemorrhoids, the proportions of fibroblasts, vascular-associated cells, and nerve cells increased, whereas epithelial cells declined, accompanied by corresponding alterations in intercellular communication. Additionally, we discovered a unique subset of GZMK⁺ CD8⁺ T cells potentially regulating the immune microenvironment via the complement signaling pathway. Overall, this study unveils the single-cell landscape of hemorrhoid tissues, providing pivotal insights that could underpin the development of targeted therapies for treating hemorrhoids and preventing recurrence.