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; Kelly A. Whelan

doi:10.1038/s41467-022-29747-x

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 TétreaultKelly A. Whelan

Cancer Signaling and Microenvironment (CSM)

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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.

Original language	English
Article number	2167
Pages (from-to)	2167
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-29747-x
State	Published - Dec 2022

Keywords

Animals
Epithelial Cells
Epithelium/metabolism
Esophageal Neoplasms/pathology
Esophagus/pathology
Humans
Mice
Single-Cell Analysis
Transcriptome/genetics

Access to Document

10.1038/s41467-022-29747-x

Cite this

Kabir, M. F., Karami, A. L., Cruz-Acuña, R., Klochkova, A., Saxena, R., Mu, A., Murray, M. G., Cruz, J., Fuller, A. D., Clevenger, M. H., Chitrala, K. N., Tan, Y., Keith, K., Madzo, J., Huang, H., Jelinek, J., Karakasheva, T., Hamilton, K. E., Muir, A. B., ... Whelan, K. A. (2022). Single cell transcriptomic analysis reveals cellular diversity of murine esophageal epithelium. Nature Communications, 13(1), 2167. Article 2167. https://doi.org/10.1038/s41467-022-29747-x

@article{c3cf498251ad4ffd8e47c6260e65c55a,

title = "Single cell transcriptomic analysis reveals cellular diversity of murine esophageal epithelium",

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.",

keywords = "Animals, Epithelial Cells, Epithelium/metabolism, Esophageal Neoplasms/pathology, Esophagus/pathology, Humans, Mice, Single-Cell Analysis, Transcriptome/genetics",

author = "Kabir, {Mohammad Faujul} and Karami, {Adam L.} and Ricardo Cruz-Acu{\~n}a and Alena Klochkova and Reshu Saxena and Anbin Mu and Murray, {Mary Grace} and Jasmine Cruz and Fuller, {Annie D.} and Clevenger, {Margarette H.} and Chitrala, {Kumaraswamy Naidu} and Yinfei Tan and Kelsey Keith and Jozef Madzo and Hugh Huang and Jaroslav Jelinek and Tatiana Karakasheva and Hamilton, {Kathryn E.} and Muir, {Amanda B.} and T{\'e}treault, {Marie Pier} and Whelan, {Kelly A.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-29747-x",

language = "English",

volume = "13",

pages = "2167",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Kabir, MF, Karami, AL, Cruz-Acuña, R, Klochkova, A, Saxena, R, Mu, A, Murray, MG, Cruz, J, Fuller, AD, Clevenger, MH, Chitrala, KN, Tan, Y, Keith, K, Madzo, J, Huang, H, Jelinek, J, Karakasheva, T, Hamilton, KE, Muir, AB, Tétreault, MP & Whelan, KA 2022, 'Single cell transcriptomic analysis reveals cellular diversity of murine esophageal epithelium', Nature Communications, vol. 13, no. 1, 2167, pp. 2167. https://doi.org/10.1038/s41467-022-29747-x

TY - JOUR

T1 - Single cell transcriptomic analysis reveals cellular diversity of murine esophageal epithelium

AU - Kabir, Mohammad Faujul

AU - Karami, Adam L.

AU - Cruz-Acuña, Ricardo

AU - Klochkova, Alena

AU - Saxena, Reshu

AU - Mu, Anbin

AU - Murray, Mary Grace

AU - Cruz, Jasmine

AU - Fuller, Annie D.

AU - Clevenger, Margarette H.

AU - Chitrala, Kumaraswamy Naidu

AU - Tan, Yinfei

AU - Keith, Kelsey

AU - Madzo, Jozef

AU - Huang, Hugh

AU - Jelinek, Jaroslav

AU - Karakasheva, Tatiana

AU - Hamilton, Kathryn E.

AU - Muir, Amanda B.

AU - Tétreault, Marie Pier

AU - Whelan, Kelly A.

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

KW - Animals

KW - Epithelial Cells

KW - Epithelium/metabolism

KW - Esophageal Neoplasms/pathology

KW - Esophagus/pathology

KW - Humans

KW - Mice

KW - Single-Cell Analysis

KW - Transcriptome/genetics

UR - http://www.scopus.com/inward/record.url?scp=85128446796&partnerID=8YFLogxK

U2 - 10.1038/s41467-022-29747-x

DO - 10.1038/s41467-022-29747-x

M3 - Article

C2 - 35443762

AN - SCOPUS:85128446796

SN - 2041-1723

VL - 13

SP - 2167

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2167

ER -

Single cell transcriptomic analysis reveals cellular diversity of murine esophageal epithelium

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Researchers reveal cellular diversity of esophageal tissue

News Cellular Diversity of Esophageal Tissue Revealed Researchers have defined 11 subsets of cells found in the esophagus of mice, information that could potentially help clinicians diagnose or treat certain types of cancer.

Lewis Katz School of Medicine at Temple University researchers reveal cellular diversity of esophageal tissue

Cite this

Single cell transcriptomic analysis reveals cellular diversity of murine esophageal epithelium

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Press/Media

Researchers reveal cellular diversity of esophageal tissue

News Cellular Diversity of Esophageal Tissue Revealed Researchers have defined 11 subsets of cells found in the esophagus of mice, information that could potentially help clinicians diagnose or treat certain types of cancer.

Lewis Katz School of Medicine at Temple University researchers reveal cellular diversity of esophageal tissue

Cite this