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

8 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

Funding

This work was supported by NIH NIDDK P01DK117824 and Digestive Health Foundation to MPT, PJK, and JEP; NIH NHLBI F31HL147413 to MHC; NIH NIDDK R01DK121159 to KAW; the Robert H. Lurie Comprehensive Cancer Center (NIH NCI CCSG P30 CA060553) through the Northwestern University Pathology Core Facility; and the NUSeq Core Facility (1S10OD025120). This research was supported in part through the computational resources and staff contributions provided for the Quest high-performance computing facility at Northwestern University, which is jointly supported by the Office of the Provost, the Office for Research, and Northwestern University Information Technology. This research was also supported in part through the computational resources and staff contributions provided by the Genomics Compute Cluster, which is jointly supported by the Feinberg School of Medicine, the Center for Genetic Medicine, Feinberg’s Department of Biochemistry and Molecular Genetics, the Office of the Provost, the Office for Research, and Northwestern Information Technology. The Genomics Compute Cluster is part of Quest, Northwestern University’s high-performance computing facility.

ASJC Scopus subject areas

  • General Medicine

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