Exosome complex orchestrates developmental signaling to balance proliferation and differentiation during erythropoiesis

  1. Skye C McIver
  2. Koichi R Katsumura
  3. Elsa Davids
  4. Peng Liu
  5. Yoon-A Kang
  6. David Yang
  7. Emery H Bresnick  Is a corresponding author
  1. University of Wisconsin School of Medicine and Public Health, United States

Abstract

Since the highly conserved exosome complex mediates the degradation and processing of multiple classes of RNAs, it almost certainly controls diverse biological processes. How this post-transcriptional RNA-regulatory machine impacts cell fate decisions and differentiation is poorly understood. Previously, we demonstrated that exosome complex subunits confer an erythroid maturation barricade, and the erythroid transcription factor GATA-1 dismantles the barricade by transcriptionally repressing the cognate genes. While dissecting requirements for the maturation barricade in Mus musculus, we discovered that the exosome complex is a vital determinant of a developmental signaling transition that dictates proliferation and amplification versus differentiation. Exosome complex integrity in erythroid precursor cells ensures Kit receptor tyrosine kinase expression and stem cell factor/Kit signaling, while preventing responsiveness to erythropoietin-instigated signals that promote differentiation. Functioning as a gatekeeper of this developmental signaling transition, the exosome complex controls the massive production of erythroid cells that ensures organismal survival in homeostatic and stress contexts.

Article and author information

Author details

  1. Skye C McIver

    Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Koichi R Katsumura

    Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Elsa Davids

    Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Peng Liu

    Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Yoon-A Kang

    Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. David Yang

    Department of Pathology, University of Wisconsin School of Medicine and Public Health, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Emery H Bresnick

    Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, United States
    For correspondence
    ehbresni@wisc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1151-5654

Funding

National Institutes of Health (DK50107)

  • Emery H Bresnick

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

Reviewing Editor

  1. Amy J Wagers, Harvard University, United States

Ethics

Animal experimentation: Example ethics statement (Chen H., et al, PLOS ONE 7(7): e41574):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 (#M02230) of the University of Wisconsin-Madison.

Version history

  1. Received: May 17, 2016
  2. Accepted: August 18, 2016
  3. Accepted Manuscript published: August 20, 2016 (version 1)
  4. Accepted Manuscript updated: September 9, 2016 (version 2)
  5. Version of Record published: September 28, 2016 (version 3)

Copyright

© 2016, McIver 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. Skye C McIver
  2. Koichi R Katsumura
  3. Elsa Davids
  4. Peng Liu
  5. Yoon-A Kang
  6. David Yang
  7. Emery H Bresnick
(2016)
Exosome complex orchestrates developmental signaling to balance proliferation and differentiation during erythropoiesis
eLife 5:e17877.
https://doi.org/10.7554/eLife.17877

Share this article

https://doi.org/10.7554/eLife.17877

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