Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation

  1. Nicolás Peláez
  2. Arnau Gavalda-Miralles
  3. Bao Wang
  4. Heliodoro Tejedor Navarro
  5. Herman Gudjonson
  6. Ilaria Rebay
  7. Aaron R Dinner
  8. Aggelos K Katsaggelos
  9. Luis AN Amaral
  10. Richard W Carthew  Is a corresponding author
  1. Northwestern University, United States
  2. Universitat Rovira i Virgili, United States
  3. Howard Hughes Medical Institute, Northwestern University, United States
  4. University of Chicago, United States

Abstract

Yan is an ETS-domain transcription factor responsible for maintaining Drosophila eye cells in a multipotent state. Using a fluorescent reporter for Yan expression, we observed a biphasic distribution of Yan in multipotent cells. Transitions to various differentiated states occurred over the course of this dynamic process, suggesting that Yan expression level does not strongly determine cell potential. Consistent with this conclusion, perturbing Yan expression by varying gene dosage had no effect on cell fate transitions. However, we observed that as cells transited to differentiation, Yan expression became highly heterogeneous and this heterogeneity was transient. Signals received via the EGF Receptor were necessary for the transience in Yan noise since genetic loss caused sustained noise. Since these signals are essential for eye cells to differentiate, we suggest that dynamic heterogeneity of Yan is a necessary element of the transition process, and cell states are stabilized through noise reduction.

Article and author information

Author details

  1. Nicolás Peláez

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Arnau Gavalda-Miralles

    Department of Chemical Engineering, Universitat Rovira i Virgili, Tarragona, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Bao Wang

    Department Electrical Engineering and Computer Science, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Heliodoro Tejedor Navarro

    Department of Chemical and Biological Engineering, Howard Hughes Medical Institute, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Herman Gudjonson

    James Franck Institute, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Ilaria Rebay

    Ben May Department for Cancer Research, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Aaron R Dinner

    James Franck Institute, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Aggelos K Katsaggelos

    Department Electrical Engineering and Computer Science, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Luis AN Amaral

    Department of Chemical and Biological Engineering, Howard Hughes Medical Institute, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Richard W Carthew

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    For correspondence
    r-carthew@northwestern.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Naama Barkai, Weizmann Institute of Science, Israel

Version history

  1. Received: May 22, 2015
  2. Accepted: November 18, 2015
  3. Accepted Manuscript published: November 19, 2015 (version 1)
  4. Version of Record published: January 13, 2016 (version 2)

Copyright

© 2015, Peláez 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. Nicolás Peláez
  2. Arnau Gavalda-Miralles
  3. Bao Wang
  4. Heliodoro Tejedor Navarro
  5. Herman Gudjonson
  6. Ilaria Rebay
  7. Aaron R Dinner
  8. Aggelos K Katsaggelos
  9. Luis AN Amaral
  10. Richard W Carthew
(2015)
Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation
eLife 4:e08924.
https://doi.org/10.7554/eLife.08924

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