Genomic insights into pediatric intestinal inflammatory and eosinophilic disorders using single-cell RNA-sequencing

Area of Science:

• Gastroenterology
• Immunology
• Molecular Biology

Background:

• Gastrointestinal inflammatory disorders, including inflammatory bowel diseases and eosinophilic disorders, cause significant tissue damage and symptoms.
• Overlapping symptoms often necessitate invasive diagnostic procedures.

Purpose of the Study:

• To investigate transcriptome alterations in peripheral blood mononuclear cells (PBMCs) from pediatric patients with gastrointestinal disorders.
• To identify potential peripheral blood biomarkers for active inflammation and diagnosis.

Main Methods:

• Single-cell RNA sequencing was performed on PBMCs from patients with Crohn's disease, ulcerative colitis, eosinophilic esophagitis, eosinophilic duodenitis, and healthy controls.
• Differential gene expression analysis was conducted across eight immune cell types.

Main Results:

• 730 differentially expressed genes (FDR < 0.05) were identified between patients and controls.
• Common patterns included widespread upregulation of MTRNR2L8.
• Distinct patterns were observed, such as XIST upregulation in ulcerative colitis and Th2-associated gene upregulation in eosinophilic disorders.

Conclusions:

• Transcriptome alterations in PBMCs reflect both shared and distinct molecular signatures across different gastrointestinal inflammatory disorders.
• These findings offer insights into potential peripheral blood-based diagnostic markers for these conditions.