Histological, immunohistochemical and transcriptomic characterization of human tracheoesophageal fistulas
Brosens, Erwin; Felix, Janine F.; Boerema-de Munck, Anne; de Jong, Elisabeth M.; Lodder, Elisabeth M.; Swagemakers, Sigrid; Buscop-van Kempen, Marjon; de Krijger, Ronald R.; Wijnen, Rene M.H.; van IJcken, Wilfred F.J.; van der Spek, Peter; de Klein, Annelies; Tibboel, Dick; Rottier, Robbert J.
(2020) PLoS ONE, volume 15, issue 11, pp. 1 - 24
(Article)
Abstract
Esophageal atresia (EA) and tracheoesophageal fistula (TEF) are relatively frequently occurring foregut malformations. EA/TEF is thought to have a strong genetic component. Not much is known regarding the biological processes disturbed or which cell type is affected in patients. This hampers the detection of the responsible culprits (genetic or environmental)
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for the origin of these congenital anatomical malformations. Therefore, we examined gene expression patterns in the TEF and compared them to the patterns in esophageal, tracheal and lung control samples. We studied tissue organization and key proteins using immunohistochemistry. There were clear differences between TEF and control samples. Based on the number of differentially expressed genes as well as histological characteristics, TEFs were most similar to normal esophagus. The BMP-signaling pathway, actin cytoskeleton and extracellular matrix pathways are downregulated in TEF. Genes involved in smooth muscle contraction are overexpressed in TEF compared to esophagus as well as trachea. These enriched pathways indicate myofibroblast activated fibrosis. TEF represents a specific tissue type with large contributions of intestinal smooth muscle cells and neurons. All major cell types present in esophagus are present-albeit often structurally disorganized-in TEF, indicating that its etiology should not be sought in cell fate specification.
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Keywords: Actin Cytoskeleton/genetics, Adult, Bone Morphogenetic Proteins/genetics, Esophagus/metabolism, Extracellular Matrix/genetics, Female, Fibrosis, Humans, Lung/metabolism, Male, Signal Transduction, Trachea/metabolism, Tracheoesophageal Fistula/genetics, Transcriptome, Journal Article, Research Support, Non-U.S. Gov't
ISSN: 1932-6203
Publisher: Public Library of Science
Note: Funding Information: This work was supported by the Edgar Doncker Foundation [DT; J.F.F.] and the Sophia Foundation for Scientific Research [Grant Numbers 493 [DT; ADK; E.M.de J.], 436 [A.de M.] and S13-09 [DT; ADK; E.B.] The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: Copyright © 2020 Brosens et al. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
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