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Characterization of 3D organotypic epithelial tissues reveals tonsil-specific differences in tonic interferon signaling

Three-dimensional (3D) culturing techniques can recapitulate the stratified nature of multicellular epithelial tissues. Organotypic 3D epithelial tissue culture methods have several applications, including the study of tissue development and function, drug discovery and toxicity testing, host-pathog...

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Autores principales: Jackson, Robert, Rajadhyaksha, Esha V, Loeffler, Reid S, Flores, Caitlyn E, Van Doorslaer, Koenraad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882319/
https://www.ncbi.nlm.nih.gov/pubmed/36711548
http://dx.doi.org/10.1101/2023.01.19.524743
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author Jackson, Robert
Rajadhyaksha, Esha V
Loeffler, Reid S
Flores, Caitlyn E
Van Doorslaer, Koenraad
author_facet Jackson, Robert
Rajadhyaksha, Esha V
Loeffler, Reid S
Flores, Caitlyn E
Van Doorslaer, Koenraad
author_sort Jackson, Robert
collection PubMed
description Three-dimensional (3D) culturing techniques can recapitulate the stratified nature of multicellular epithelial tissues. Organotypic 3D epithelial tissue culture methods have several applications, including the study of tissue development and function, drug discovery and toxicity testing, host-pathogen interactions, and the development of tissue-engineered constructs for use in regenerative medicine. We grew 3D organotypic epithelial tissues from foreskin, cervix, and tonsil-derived primary cells and characterized the transcriptome of these in vitro tissue equivalents. Using the same 3D culturing method, all three tissues yielded stratified squamous epithelium, validated histologically using basal and superficial epithelial cell markers. The goal of this study was to use RNA-seq to compare gene expression patterns in these three types of epithelial tissues to gain a better understanding of the molecular mechanisms underlying their function and identify potential therapeutic targets for various diseases. Functional profiling by over-representation and gene set enrichment analysis revealed tissue-specific differences: i.e., cutaneous homeostasis and lipid metabolism in foreskin, extracellular matrix remodeling in cervix, and baseline innate immune differences in tonsil. Specifically, tonsillar epithelia may play an active role in shaping the immune microenvironment of the tonsil balancing inflammation and immune responses in the face of constant exposure to microbial insults. Overall, these data serve as a resource, with gene sets made available for the research community to explore, and as a foundation for understanding the epithelial heterogeneity and how it may impact their in vitro use. An online resource is available to investigate these data (https://viz.datascience.arizona.edu/3DEpiEx/).
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spelling pubmed-98823192023-01-28 Characterization of 3D organotypic epithelial tissues reveals tonsil-specific differences in tonic interferon signaling Jackson, Robert Rajadhyaksha, Esha V Loeffler, Reid S Flores, Caitlyn E Van Doorslaer, Koenraad bioRxiv Article Three-dimensional (3D) culturing techniques can recapitulate the stratified nature of multicellular epithelial tissues. Organotypic 3D epithelial tissue culture methods have several applications, including the study of tissue development and function, drug discovery and toxicity testing, host-pathogen interactions, and the development of tissue-engineered constructs for use in regenerative medicine. We grew 3D organotypic epithelial tissues from foreskin, cervix, and tonsil-derived primary cells and characterized the transcriptome of these in vitro tissue equivalents. Using the same 3D culturing method, all three tissues yielded stratified squamous epithelium, validated histologically using basal and superficial epithelial cell markers. The goal of this study was to use RNA-seq to compare gene expression patterns in these three types of epithelial tissues to gain a better understanding of the molecular mechanisms underlying their function and identify potential therapeutic targets for various diseases. Functional profiling by over-representation and gene set enrichment analysis revealed tissue-specific differences: i.e., cutaneous homeostasis and lipid metabolism in foreskin, extracellular matrix remodeling in cervix, and baseline innate immune differences in tonsil. Specifically, tonsillar epithelia may play an active role in shaping the immune microenvironment of the tonsil balancing inflammation and immune responses in the face of constant exposure to microbial insults. Overall, these data serve as a resource, with gene sets made available for the research community to explore, and as a foundation for understanding the epithelial heterogeneity and how it may impact their in vitro use. An online resource is available to investigate these data (https://viz.datascience.arizona.edu/3DEpiEx/). Cold Spring Harbor Laboratory 2023-01-20 /pmc/articles/PMC9882319/ /pubmed/36711548 http://dx.doi.org/10.1101/2023.01.19.524743 Text en https://creativecommons.org/licenses/by-nc/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Jackson, Robert
Rajadhyaksha, Esha V
Loeffler, Reid S
Flores, Caitlyn E
Van Doorslaer, Koenraad
Characterization of 3D organotypic epithelial tissues reveals tonsil-specific differences in tonic interferon signaling
title Characterization of 3D organotypic epithelial tissues reveals tonsil-specific differences in tonic interferon signaling
title_full Characterization of 3D organotypic epithelial tissues reveals tonsil-specific differences in tonic interferon signaling
title_fullStr Characterization of 3D organotypic epithelial tissues reveals tonsil-specific differences in tonic interferon signaling
title_full_unstemmed Characterization of 3D organotypic epithelial tissues reveals tonsil-specific differences in tonic interferon signaling
title_short Characterization of 3D organotypic epithelial tissues reveals tonsil-specific differences in tonic interferon signaling
title_sort characterization of 3d organotypic epithelial tissues reveals tonsil-specific differences in tonic interferon signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882319/
https://www.ncbi.nlm.nih.gov/pubmed/36711548
http://dx.doi.org/10.1101/2023.01.19.524743
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