The transcription factor scleraxis differentially regulates gene expression in tenocytes isolated at different developmental stages. (September 2020)

• Record Type: Journal Article
• Authors: Paterson, Y.Z.; Evans, N.; Kan, S.; Cribbs, A.; Henson, F.M.D.; Guest, D.J.
• Is Part Of: Mechanisms of development. Volume 163(2020)
• Publication Date: 2020-09
• Subjects: Scleraxis -- Gene regulation -- Tendon development -- Transcriptomics -- Knockdown -- Chromatin Immunoprecipitation; Developmental biology -- Periodicals; Molecular biology -- Periodicals; Developmental Biology -- Periodicals; Molecular Biology -- Periodicals; Biologie du développement -- Périodiques; Biologie moléculaire -- Périodiques; Developmental biology; Molecular biology; Periodicals; Electronic journals; 571.8
• DOI: 10.1016/j.mod.2020.103635
• Languages: English
• ISSNs: 0925-4773

Abstract

Abstract: The transcription factor scleraxis (SCX) is expressed throughout tendon development and plays a key role in directing tendon wound healing. However, little is known regarding its role in fetal or young postnatal tendons, stages in development that are known for their enhanced regenerative capabilities. Here we used RNA-sequencing to compare the transcriptome of adult and fetal tenocytes following SCX knockdown. SCX knockdown had a larger effect on gene expression in fetal tenocytes, affecting 477 genes in comparison to the 183 genes affected in adult tenocytes, indicating that scleraxis-dependent processes may differ in these two developmental stages. Gene ontology, network and pathway analysis revealed an overrepresentation of extracellular matrix (ECM) remodelling processes within both comparisons. These included several matrix metalloproteinases, proteoglycans and collagens, some of which were also investigated in SCX knockdown tenocytes from young postnatal foals. Using chromatin immunoprecipitation, we also identified novel genes that SCX differentially interacts with in adult and fetal tenocytes. These results indicate a role for SCX in modulating ECM synthesis and breakdown and provide a useful dataset for further study into SCX gene regulation. Graphical abstract: Unlabelled Image Highlights: Scleraxis-dependent gene expression is differentially controlled in adult and fetal tenocytes. Scleraxis knockdown results in changes in extracellular matrix remodelling genes. Chromatin immunoprecipitation reveals novel downstream target genes which scleraxis directly regulates.