Single cell transcriptomic analysis reveals cellular diversity of murine esophageal epithelium

Although morphologic progression coupled with expression of specific molecular markers has been characterized along the esophageal squamous differentiation gradient, the molecular heterogeneity within cell types along this trajectory has yet to be classified at the single cell level. To address this knowledge gap, we perform single cell RNA-sequencing of 44,679 murine esophageal epithelial, to identify 11 distinct cell populations as well as pathways alterations along the basal-superficial axis and in each individual population. We evaluate the impact of aging upon esophageal epithelial cell populations and demonstrate age-associated mitochondrial dysfunction. We compare single cell transcriptomic profiles in 3D murine organoids and human esophageal biopsies with that of murine esophageal epithelium. Finally, we employ pseudotemporal trajectory analysis to develop a working model of cell fate determination in murine esophageal epithelium. These studies provide comprehensive molecular perspective on the cellular heterogeneity of murine esophageal epithelium in the context of homeostasis and aging. The level of cellular diversity in the esophageal epithelium has yet to be classified at the single cell level. Here the authors analyze the transcriptome of 44,679 murine esophageal keratinocytes to identify an unexpected level of cellular heterogeneity.

Automated summary

This study uses single cell RNA sequencing to analyze 44,679 murine esophageal epithelial cells, identifying 11 distinct cell populations and studying their pathway alterations along the basal-superficial axis and within each population. The study also reveals the impact of aging on esophageal epithelial cell populations and their association with mitochondrial dysfunction. By comparing single cell transcriptomic profiles of 3D murine organoids, human esophageal biopsies, and murine esophageal epithelium, a working model of cell fate determination in the murine esophageal epithelium is developed. These findings provide a comprehensive molecular perspective on the cellular heterogeneity of murine esophageal epithelium in the context of homeostasis and aging.