Single cell transcriptomic analysis reveals cellular diversity of murine esophageal epithelium

Mohammad Faujul Kabir, Adam L. 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 Madzo, Hugh Huang, Jaroslav Jelinek, Tatiana Karakasheva, Kathryn E. Hamilton, Amanda B. Muir, Marie-Pier Tétreault and Kelly A. Whelan ()
Additional contact information
Mohammad Faujul Kabir: Temple University Lewis Katz School of Medicine
Adam L. Karami: Temple University Lewis Katz School of Medicine
Ricardo Cruz-Acuña: Columbia University Medical Center
Alena Klochkova: Temple University Lewis Katz School of Medicine
Reshu Saxena: Temple University Lewis Katz School of Medicine
Anbin Mu: Temple University Lewis Katz School of Medicine
Mary Grace Murray: Temple University Lewis Katz School of Medicine
Jasmine Cruz: Temple University Lewis Katz School of Medicine
Annie D. Fuller: Temple University Lewis Katz School of Medicine
Margarette H. Clevenger: Northwestern University Feinberg School of Medicine
Kumaraswamy Naidu Chitrala: Temple University Lewis Katz School of Medicine
Yinfei Tan: Fox Chase Cancer Center
Kelsey Keith: Coriell Institute for Medical Research
Jozef Madzo: Coriell Institute for Medical Research
Hugh Huang: Coriell Institute for Medical Research
Jaroslav Jelinek: Coriell Institute for Medical Research
Tatiana Karakasheva: Children’s Hospital of Philadelphia
Kathryn E. Hamilton: Children’s Hospital of Philadelphia
Amanda B. Muir: Children’s Hospital of Philadelphia
Marie-Pier Tétreault: Northwestern University Feinberg School of Medicine
Kelly A. Whelan: Temple University Lewis Katz School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29747-x

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