Department of Pediatric Surgery, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China.
Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fujian, China.
BMC Med. 2024 Sep 12;22(1):383. doi: 10.1186/s12916-024-03611-9.
The 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.
We 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.
Our 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.
Our study provides new insights into the development of the appendix and deepens the understanding of appendicitis in preschool children.
人类阑尾在细胞水平上的发育及其功能尚未得到很好的理解。尽管学龄前儿童阑尾炎不常见，但穿孔率高，发病率增加。
我们对胎儿和儿童期以及学龄前炎症性阑尾进行了单细胞 RNA 测序 (scRNA-seq)。讨论了发育中阑尾中每个细胞区室的转录特征。还研究了细胞间相互作用和分化轨迹。我们将学龄前阑尾炎的 scRNA-seq 图谱与匹配的健康对照组进行比较，以揭示与疾病相关的变化。使用批量转录组数据、免疫组织化学和实时定量 PCR 来验证发现。
我们的分析总共鉴定出 76 种细胞类型，并描述了发育中阑尾的细胞图谱。我们发现 BMP 信号通路在阑尾上皮发育中的潜在作用，并鉴定出 HOXC8 和 PITX2 是阑尾杯状细胞的特定调节子。在学龄前阑尾中发现了更高的周细胞覆盖率、内皮血管生成和杯状粘液评分，以及更低的上皮和内皮紧密连接评分，这可能有助于学龄前阑尾炎的临床特征。学龄前阑尾炎 scRNA-seq 图谱显示，白细胞介素 17 信号通路可能参与炎症过程。
我们的研究为阑尾的发育提供了新的见解，并加深了对学龄前儿童阑尾炎的理解。
