Single cell transcriptomic analysis reveals cellular diversity of murine esophageal epithelium
Mohammad Faujul Kabir, Adam Karami, Ricardo Cruz‐Acuña, Alena Klochkova, Reshu Saxena, Anbin Mu, Mary Grace Murray, Jasmine Cruz, Annie D. Fuller, Margarette H. Clevenger, Kumaraswamy Naidu Chitrala, Yinfei Tan, Kelsey Keith, Jozef Madžo, Hugh H. Huang, Jaroslav Jelı́nek, Tatiana A. Karakasheva, Kathryn E. Hamilton, Amanda B. Muir, Marie‐Pier Tétreault, Kelly A. Whelan
Abstract
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.