Single-cell RNA-Seq of human esophageal epithelium in homeostasis and allergic inflammation
Mark Rochman, Ting Wen, Michael Kotliar, Phillip J. Dexheimer, Netali Ben-Baruch Morgenstern, Julie M. Caldwell, Hee-Woong Lim, Marc E. Rothenberg
Mark Rochman, Ting Wen, Michael Kotliar, Phillip J. Dexheimer, Netali Ben-Baruch Morgenstern, Julie M. Caldwell, Hee-Woong Lim, Marc E. Rothenberg
View: Text | PDF
Research Article Immunology Inflammation

Single-cell RNA-Seq of human esophageal epithelium in homeostasis and allergic inflammation

Abstract

Inflammation of the esophageal epithelium is a hallmark of eosinophilic esophagitis (EoE), an emerging chronic allergic disease. Herein, we probed human esophageal epithelial cells at single-cell resolution during homeostasis and EoE. During allergic inflammation, the epithelial differentiation program was blocked, leading to loss of KRT6hi differentiated populations and expansion of TOP2hi proliferating, DSPhi transitioning, and SERPINB3hi transitioning populations; however, there was stability of the stem cell–enriched PDPNhi basal epithelial compartment. This differentiation program blockade was associated with dysregulation of transcription factors, including nuclear receptor signalers, in the most differentiated epithelial cells and altered NOTCH-related cell-to-cell communication. Each epithelial population expressed genes with allergic disease risk variants, supporting their functional interplay. The esophageal epithelium differed notably between EoE in histologic remission and controls, indicating that remission is a transitory state poised to relapse. Collectively, our data uncover the dynamic nature of the inflamed human esophageal epithelium and provide a framework to better understand esophageal health and disease.

Authors

Mark Rochman, Ting Wen, Michael Kotliar, Phillip J. Dexheimer, Netali Ben-Baruch Morgenstern, Julie M. Caldwell, Hee-Woong Lim, Marc E. Rothenberg

×

Figure 1

Single-cell analysis of human esophageal biopsies delineating major esophageal cell types.

Options: View larger image (or click on image) Download as PowerPoint
Single-cell analysis of human esophageal biopsies delineating major esop...
(A) Schematic representation of the experimental design and the uniform manifold approximation and projection (UMAP) of all samples depicting major cell types from the esophageal biopsies. n = 2, healthy controls (normal); n = 3, EoE in remission (remission); n = 5, active EoE inflammation (active). (B) Marker gene expression heatmap of major cell types and top 10 representative genes per cell type. Each column represents a single cell, and each row represents an individual gene. (C) Quantification of the cell types and comparison of their proportion by disease status. *P = 0.06; **P < 0.05; 2-tailed Student’s t test. Data are shown as mean ± SD. (D) Heatmap of average expression of all 10 samples for top 50 upregulated and downregulated genes from the bulk RNA-Seq EoE transcriptome (6) stratified by the cell type.