• Lingdu Meng, Yifan Yang, Shiwei He, Huifen Chen, Yong Zhan, Ran Yang, Zifeng Li, Jiajie Zhu, Jin Zhou, Yi Li, Lulu Xie, Gong Chen, Shan Zheng, Xiaoying Yao, and Rui Dong.
• Department of Pediatric Surgery, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China.
• Bmc Med. 2024 Sep 12; 22 (1): 383383.

BackgroundThe development of the human vermiform appendix at the cellular level, as well as its function, is not well understood. Appendicitis in preschool children, although uncommon, is associated with a high perforation rate and increased morbidity.MethodsWe performed single-cell RNA sequencing (scRNA-seq) on the human appendix during fetal and pediatric stages as well as preschool-age inflammatory appendices. Transcriptional features of each cell compartment were discussed in the developing appendix. Cellular interactions and differentiation trajectories were also investigated. We compared scRNA-seq profiles from preschool appendicitis to those of matched healthy controls to reveal disease-associated changes. Bulk transcriptomic data, immunohistochemistry, and real-time quantitative PCR were used to validate the findings.ResultsOur analysis identified 76 cell types in total and described the cellular atlas of the developing appendix. We discovered the potential role of the BMP signaling pathway in appendiceal epithelium development and identified HOXC8 and PITX2 as the specific regulons of appendix goblet cells. Higher pericyte coverage, endothelial angiogenesis, and goblet mucus scores together with lower epithelial and endothelial tight junction scores were found in the preschool appendix, which possibly contribute to the clinical features of preschool appendicitis. Preschool appendicitis scRNA-seq profiles revealed that the interleukin-17 signaling pathway may participate in the inflammation process.ConclusionsOur study provides new insights into the development of the appendix and deepens the understanding of appendicitis in preschool children.© 2024. The Author(s).

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