YAP regulates cell size and growth dynamics via non-cell autonomous mediators

Abstract

The Hippo pathway regulates organ size, regeneration, and cell growth by controlling the stability of the transcription factor, YAP (Yorkie in Drosophila). When there is tissue damage, YAP is activated allowing the restoration of homeostatic tissue size. The exact signals by which YAP is activated are still not fully understood, but its activation is known to affect both cell size and cell number. Here we used cultured cells to examine the coordinated regulation of cell size and number under the control of YAP. Our experiments in isogenic HEK293 cells reveal that YAP can affect cell size and number by independent circuits. Some of these effects are cell autonomous, such as proliferation, while others are mediated by secreted signals. In particular CYR61, a known secreted YAP target, is a non-cell autonomous mediator of cell survival, while another unidentified secreted factor controls cell size.

Data availability

Sequencing data has been deposited in GEO under accession code GSE123296

The following data sets were generated

Article and author information

Author details

  1. Douaa Mugahid

    Department of Systems Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Marian Kalocsay

    Department of Systems Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Xili Liu

    Department of Systems Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jonathan Scott Gruver

    Department of Systems Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Leonid Peshkin

    Department of Systems Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6420-848X
  6. Marc W Kirschner

    Department of Systems Biology, Harvard Medical School, Boston, United States
    For correspondence
    marc@hms.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6540-6130

Funding

Harvard Medical School (Dean's Innovation Grant)

  • Marc W Kirschner

National Institute of General Medical Sciences (GM026875)

  • Marc W Kirschner

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Duojia Pan, UT Southwestern Medical Center and HHMI, United States

Publication history

  1. Received: November 7, 2019
  2. Accepted: December 16, 2019
  3. Accepted Manuscript published: January 8, 2020 (version 1)
  4. Accepted Manuscript updated: January 9, 2020 (version 2)
  5. Version of Record published: January 29, 2020 (version 3)
  6. Version of Record updated: January 30, 2020 (version 4)

Copyright

© 2020, Mugahid 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. Douaa Mugahid
  2. Marian Kalocsay
  3. Xili Liu
  4. Jonathan Scott Gruver
  5. Leonid Peshkin
  6. Marc W Kirschner
(2020)
YAP regulates cell size and growth dynamics via non-cell autonomous mediators
eLife 9:e53404.
https://doi.org/10.7554/eLife.53404

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