Single cell transcriptomic analysis reveals cellular diversity of murine esophageal epithelium

• Published in: Nature communications 2022-04, Vol.13 (1), p.2167-2167, Article 2167
• Main Authors: Kabir, Mohammad Faujul, Karami, Adam L., Cruz-Acuña, Ricardo, Klochkova, Alena, Saxena, Reshu, Mu, Anbin, Murray, Mary Grace, Cruz, Jasmine, Fuller, Annie D., Clevenger, Margarette H., Chitrala, Kumaraswamy Naidu, Tan, Yinfei, Keith, Kelsey, Madzo, Jozef, Huang, Hugh, Jelinek, Jaroslav, Karakasheva, Tatiana, Hamilton, Kathryn E., Muir, Amanda B., Tétreault, Marie-Pier, Whelan, Kelly A.
• Format: Article
• Language: English
• Subjects: 13; 13/106; 13/51; 14; 14/32; 38; 38/32; 38/91; 45; 631/1647/514/1949; 631/337/2019; 631/61/212/2019; 64; Aging; Animals; Biopsy; Cell fate; Epithelial Cells; Epithelium; Epithelium - metabolism; Esophageal Neoplasms - pathology; Esophagus; Esophagus - pathology; Gene sequencing; Heterogeneity; Homeostasis; Humanities and Social Sciences; Humans; Keratinocytes; Mice; Mitochondria; multidisciplinary; Organoids; Populations; Science; Science (multidisciplinary); Single-Cell Analysis; Trajectory analysis; Transcriptome - genetics; Transcriptomes; Transcriptomics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-29747-x

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.