Suprabasal cells retain progenitor cell identity programs in eosinophilic esophagitis–driven basal cell hyperplasia

Margarette H. Clevenger, Adam L. Karami, Dustin A. Carlson, Peter J. Kahrilas, Nirmala Gonsalves, John E. Pandolfino, Deborah R. Winter, Kelly A. Whelan, Marie Pier Tétreault*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Eosinophilic esophagitis (EoE) is an esophageal immune-mediated disease characterized by eosinophilic inflammation and epithelial remodeling, including basal cell hyperplasia (BCH). Although BCH is known to correlate with disease severity and with persistent symptoms in patients in histological remission, the molecular processes driving BCH remain poorly defined. Here, we demonstrate that BCH is predominantly characterized by an expansion of nonproliferative suprabasal cells that are still committed to early differentiation. Furthermore, we discovered that suprabasal and superficial esophageal epithelial cells retain progenitor identity programs in EoE, evidenced by increased quiescent cell identity scoring and the enrichment of signaling pathways regulating stem cell pluripotency. Enrichment and trajectory analyses identified SOX2 and KLF5 as potential drivers of the increased quiescent identity and epithelial remodeling observed in EoE. Notably, these alterations were not observed in gastroesophageal reflux disease. These findings provide additional insights into the differentiation process in EoE and highlight the distinct characteristics of suprabasal and superficial esophageal epithelial cells in the disease.

Original languageEnglish (US)
Article numbere171765
JournalJCI Insight
Volume8
Issue number19
DOIs
StatePublished - Oct 2023

ASJC Scopus subject areas

  • General Medicine

Fingerprint

Dive into the research topics of 'Suprabasal cells retain progenitor cell identity programs in eosinophilic esophagitis–driven basal cell hyperplasia'. Together they form a unique fingerprint.

Cite this