The transcription factor scleraxis differentially regulates gene expression in tenocytes isolated at different developmental stages.
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.
Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.
Publication Date: 2020-08-11 PubMed ID: 32795590DOI: 10.1016/j.mod.2020.103635Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study focuses on the role of the transcription factor scleraxis (SCX) in tendon development, particularly in fetal or young postnatal tendons, by comparing the transcriptome of adult and fetal tenocytes following SCX knockdown, which led to the discovery of new genes that interact with SCX in different developmental stages.
Objective of the Research
- The main objective of the study was to explore the role of the transcription factor scleraxis (SCX) in the development of tendons, especially during fetal and young postnatal stages. The researchers wanted to understand how SCX differentially regulates gene expression during these key developmental stages.
Methods Used
- The authors used RNA-sequencing to compare the transcriptomes of adult and fetal tenocytes (cells involved in tendon development) following a reduction in SCX activity, referred to as SCX knockdown.
- Gene ontology, network, and pathway analysis tools were employed to examine the affected genes and the processes they are involved in.
- They also used chromatin immunoprecipitation, which is a technique for assessing protein-to-DNA interactions, to identify new genes that interact with SCX differently in fetal and adult tenocytes.
Key Findings
- SCX knockdown had a larger impact on gene expression in fetal tenocytes, affecting 477 genes compared to 183 in adult tenocytes. This suggests that scleraxis-dependent processes may vary in these two developmental stages.
- Upon analysis, these affected genes were found to be majorly involved in extracellular matrix (ECM) remodeling activities in both comparisons.
- Interestingly, the researchers observed SCX’s interaction with a number of new genes in adult and fetal tenocytes, indicating that SCX may also play a role in modulating ECM synthesis and breakdown.
Implications
- The study’s results can be crucial in gaining a deeper understanding of tendon development and wound healing, potentially leading to the development of new treatments for tendon injuries.
- Furthermore, the dataset made available by this study could prove helpful for other researchers studying SCX gene regulation and its impact on ECM remodeling.
Cite This Article
APA
Paterson YZ, Evans N, Kan S, Cribbs A, Henson FMD, Guest DJ.
(2020).
The transcription factor scleraxis differentially regulates gene expression in tenocytes isolated at different developmental stages.
Mech Dev, 163, 103635.
https://doi.org/10.1016/j.mod.2020.103635 Publication
Researcher Affiliations
- Department of Veterinary Medicine, University of Cambridge, Cambridge, UK; Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK. Electronic address: yzp20@cam.ac.uk.
- Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK. Electronic address: nevans5@rvc.ac.uk.
- Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK. Electronic address: skan3@sheffield.ac.uk.
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK. Electronic address: adam.cribbs@ndorms.ox.ac.uk.
- Department of Veterinary Medicine, University of Cambridge, Cambridge, UK; Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK. Electronic address: fmdh1@cam.ac.uk.
- Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK; Deptartment of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts AL9 7TA, UK. Electronic address: djguest@rvc.ac.uk.
MeSH Terms
- Animals
- Basic Helix-Loop-Helix Transcription Factors / genetics
- Collagen / genetics
- Extracellular Matrix / genetics
- Gene Expression Regulation / genetics
- Horses / genetics
- Horses / growth & development
- RNA, Messenger / genetics
- RNA-Seq
- Tendon Injuries / genetics
- Tendon Injuries / pathology
- Tendons / growth & development
- Tendons / pathology
- Tenocytes / metabolism
- Tenocytes / pathology
- Transcription Factors / genetics
- Transcriptome / genetics
- Wound Healing / genetics
Grant Funding
- Biotechnology and Biological Sciences Research Council
Conflict of Interest Statement
Declaration of competing interest None.
Citations
This article has been cited 4 times.- Subramanian A, Nayak PK, Miller CL, Dranow DB, Roberts RR, Crump JG, Schilling TF. Analysis of cranial tenocyte heterogeneity reveals a role for Wnt signaling in tendon attachments. Development 2026 Jan 15;153(2).
- Alsaigh T, Evans D, Frankel D, Torkamani A. Decoding the transcriptome of calcified atherosclerotic plaque at single-cell resolution. Commun Biol 2022 Oct 12;5(1):1084.
- Liu H, Xu J, Lan Y, Lim HW, Jiang R. The Scleraxis Transcription Factor Directly Regulates Multiple Distinct Molecular and Cellular Processes During Early Tendon Cell Differentiation. Front Cell Dev Biol 2021;9:654397.
- Best KT, Korcari A, Mora KE, Nichols AE, Muscat SN, Knapp E, Buckley MR, Loiselle AE. Scleraxis-lineage cell depletion improves tendon healing and disrupts adult tendon homeostasis. Elife 2021 Jan 22;10.
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