Journal Article

Histological, immunohistochemical and transcriptomic characterization of human tracheoesophageal fistulas

Lodder, Elisabeth M., Wijnen, Rene M. H., Tibboel, Dick, Brosens, Erwin, de Klein, Annelies, de Jong, Elisabeth M., van IJcken, Wilfred F. J., de Krijger, Ronald R., Buscop-van Kempen, Marjon, Swagemakers, Sigrid, Felix, Janine F., Boerema-de Munck, Anne, van der Spek, Peter, Rottier, Robbert J.

2020

Overview

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) 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Actin / Actin Cytoskeleton - genetics / Actin Cytoskeleton - metabolism / Adult / Bioinformatics / Biological activity / Biology / Biology and Life Sciences / Bone Morphogenetic Proteins - genetics / Bone Morphogenetic Proteins - metabolism / Causes of / Cell fate / Congenital defects / Congenital diseases / Cytoskeleton / Diagnosis / Diagnostic immunohistochemistry / Digestive system abnormalities / Esophagus / Esophagus - metabolism / Esophagus - pathology / Etiology / Extracellular matrix / Extracellular Matrix - genetics / Extracellular Matrix - metabolism / Female / Fibrosis / Foregut / Gene expression / Genes / Genetic aspects / Genetics / Gestational age / Hospitals / Humans / Immunohistochemistry / Intestine / Lung - metabolism / Male / Medicine and Health Sciences / Muscle contraction / Muscles / Muscular function / Pathology / Patients / Pediatrics / Signal Transduction / Smooth muscle / Surgery / Trachea / Trachea - metabolism / Tracheoesophageal fistula / Tracheoesophageal Fistula - genetics / Tracheoesophageal Fistula - metabolism / Tracheoesophageal Fistula - pathology / Transcriptome