TGFβ signaling is critical for maintenance of the tendon cell fate
Studies of cell fate focus on specification, but little is known about maintenance of the differentiated state. In this study we find that the mouse tendon cell fate requires continuous maintenance in vivo and identify an essential role for TGFβ signaling in maintenance of the tendon cell fate. To examine the role of TGFβ signaling in tenocyte function the TGFb type II receptor (Tgfbr2) was targeted in the Scleraxis-expressing cell lineage using the ScxCre deletor. Tendon development was not disrupted in mutant embryos, but shortly after birth tenocytes lost differentiation markers and reverted to a more stem/progenitor state. Viral reintroduction of Tgfbr2 to mutants prevented and even rescued tenocyte dedifferentiation suggesting a continuous and cell autonomous role for TGFβ signaling in cell fate maintenance. These results uncover the critical importance of molecular pathways that maintain the differentiated cell fate and a key role for TGFβ signaling in these processes.
All data generated or analyzed during this study are included in the manuscript and Supplementary Files.Single cell RNA-Seq data has been deposited onto GEO under accession code GSE139558.
Differentially expressed transcriptomes of P7 mouse tendon cells with targeted deletion of TGF-beta signalingNCBI Gene Expression Omnibus, GSE139558.
Article and author information
National Institutes of Health (R01AR055973)
- Ronen Schweitzer
Shriners Hospitals for Children (SHC 5410-POR-14)
- Ronen Schweitzer
National Institutes of Health (R01DC014160)
- John V Brigande
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (IP00000717) of the Oregon Health & Science University.
- Cheryl Ackert-Bicknell, University of Colorado, United States
- Received: October 12, 2019
- Accepted: January 17, 2020
- Accepted Manuscript published: January 21, 2020 (version 1)
- Version of Record published: February 17, 2020 (version 2)
© 2020, Tan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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