TY - JOUR
T1 - Histological, immunohistochemical and transcriptomic characterization of human tracheoesophageal fistulas
AU - Brosens, Erwin
AU - Felix, Janine F.
AU - Boerema-De Munck, Anne
AU - De Jong, Elisabeth M.
AU - Lodder, Elisabeth M.
AU - Swagemakers, Sigrid
AU - Buscop-Van Kempen, Marjon
AU - De Krijger, Ronald R.
AU - Wijnen, Rene M.H.
AU - Van IJcken, Wilfred F.J.
AU - Van Der Spek, Peter
AU - De Klein, Annelies
AU - Tibboel, Dick
AU - Rottier, Robbert J.
N1 - Publisher Copyright:
Copyright © 2020 Brosens et al.
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85096348581&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0242167
DO - 10.1371/journal.pone.0242167
M3 - Article
C2 - 33201890
AN - SCOPUS:85096348581
SN - 1932-6203
VL - 15
JO - PLoS ONE
JF - PLoS ONE
IS - 11 November
M1 - e0242167
ER -