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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1420208
This article is part of the Research Topic Understanding Molecular Mechanisms to Facilitate the Development of Biomarkers for Therapeutic Intervention in Gastrointestinal Diseases and Sepsis View all 7 articles

Genomic Insights into Pediatric Intestinal Inflammatory and Eosinophilic Disorders using Single-cell RNA-sequencing

Provisionally accepted
Marissa R. Keever-Keigher Marissa R. Keever-Keigher 1Lisa Harvey Lisa Harvey 1Veronica Williams Veronica Williams 1Carrie A. Vyhlidal Carrie A. Vyhlidal 2Atif A. Ahmed Atif A. Ahmed 3Jeffery J. Johnston Jeffery J. Johnston 1Daniel A. Louiselle Daniel A. Louiselle 1Elin Grundberg Elin Grundberg 1,4Tomi Pastinen Tomi Pastinen 1,4Craig A. Friesen Craig A. Friesen 1,4Rachel Chevalier Rachel Chevalier 1,4Craig Smail Craig Smail 1,4*Valentina Shakhnovich Valentina Shakhnovich 5
  • 1 Children's Research Institute, Children's Mercy Hospital, Kansas City, United States
  • 2 KCAS Bioanalytical & Biomarker Services, Shawnee, United States
  • 3 Seattle Children's Hospital-University of Washington, Seattle, United States
  • 4 School of Medicine, University of Missouri–Kansas City, Kansas City, Kansas, United States
  • 5 Ironwood Pharmaceuticals, Boston, United States

The final, formatted version of the article will be published soon.

    Chronic inflammation of the gastrointestinal tissues underlies gastrointestinal inflammatory disorders, leading to tissue damage and a constellation of painful and debilitating symptoms. These disorders include inflammatory bowel diseases (Crohn's disease and ulcerative colitis), and eosinophilic disorders (eosinophilic esophagitis and eosinophilic duodenitis). Gastrointestinal inflammatory disorders can often present with overlapping symptoms necessitating the use of invasive procedures to give an accurate diagnosis. This study used peripheral blood mononuclear cells from individuals with Crohn's disease, ulcerative colitis, eosinophilic esophagitis, and eosinophilic duodenitis to better understand the alterations to the transcriptome of individuals with these diseases and identify potential markers of active inflammation within the peripheral blood of patients that may be useful in diagnosis. Single-cell RNA-sequencing was performed on peripheral blood mononuclear cells isolated from the blood samples of pediatric patients diagnosed with gastrointestinal disorders, including Crohn's disease, ulcerative colitis, eosinophilic esophagitis, eosinophilic duodenitis, and controls with histologically healthy gastrointestinal tracts. We identified 730 (FDR < 0.05) differentially expressed genes between individuals with gastrointestinal disorders and controls across eight immune cell types. There were common patterns among GI disorders, such as the widespread upregulation of MTRNR2L8 across cell types, and many differentially expressed genes showed distinct patterns of dysregulation among the different gastrointestinal diseases compared to controls, including upregulation of XIST across cell types among individuals with ulcerative colitis and upregulation of Th2-associated genes in eosinophilic disorders. These findings indicate both overlapping and distinct alterations to the transcriptome of individuals with gastrointestinal disorders compared to controls, which provide insight as to which genes may be useful as markers for disease in the peripheral blood of patients.

    Keywords: single-cell, RNA-Seq, Gastrointestinal disorder, Pediatrics, Genomics

    Received: 19 Apr 2024; Accepted: 26 Jul 2024.

    Copyright: © 2024 Keever-Keigher, Harvey, Williams, Vyhlidal, Ahmed, Johnston, Louiselle, Grundberg, Pastinen, Friesen, Chevalier, Smail and Shakhnovich. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Craig Smail, Children's Research Institute, Children's Mercy Hospital, Kansas City, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.