TGFβ signaling is critical for maintenance of the tendon cell fate

  1. Guak-Kim Tan
  2. Brian A Pryce
  3. Anna Stabio
  4. John V Brigande
  5. ChaoJie Wang
  6. Zheng Xia
  7. Sara F Tufa
  8. Douglas R Keene
  9. Ronen Schweitzer  Is a corresponding author
  1. Shriners Hospitals for Children, United States
  2. Oregon Health and Science University, United States

Abstract

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.

Data availability

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.

The following data sets were generated

Article and author information

Author details

  1. Guak-Kim Tan

    Research Division, Shriners Hospitals for Children, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Brian A Pryce

    Research Division, Shriners Hospitals for Children, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Anna Stabio

    Research Division, Shriners Hospitals for Children, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. John V Brigande

    Oregon Hearing Research Center, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. ChaoJie Wang

    Computational Biology Program, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Zheng Xia

    Computational Biology Program, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Sara F Tufa

    Research Division, Shriners Hospitals for Children, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Douglas R Keene

    Research Division, Shriners Hospitals for Children, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Ronen Schweitzer

    Research Division, Shriners Hospitals for Children, Portland, United States
    For correspondence
    schweitz@ohsu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7425-5028

Funding

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.

Ethics

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.

Reviewing Editor

  1. Cheryl Ackert-Bicknell, University of Colorado, United States

Publication history

  1. Received: October 12, 2019
  2. Accepted: January 17, 2020
  3. Accepted Manuscript published: January 21, 2020 (version 1)
  4. Version of Record published: February 17, 2020 (version 2)

Copyright

© 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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  1. Guak-Kim Tan
  2. Brian A Pryce
  3. Anna Stabio
  4. John V Brigande
  5. ChaoJie Wang
  6. Zheng Xia
  7. Sara F Tufa
  8. Douglas R Keene
  9. Ronen Schweitzer
(2020)
TGFβ signaling is critical for maintenance of the tendon cell fate
eLife 9:e52695.
https://doi.org/10.7554/eLife.52695
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