1. Stem Cells and Regenerative Medicine
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Sequential activation of transcriptional repressors promotes progenitor commitment by silencing stem cell identity genes

  1. Noemi Rives- Quinto
  2. Hideyuki Komori
  3. Cyrina M Ostgaard
  4. Derek H Janssens
  5. Shu Kondo
  6. Qi Dai
  7. Adrian W Moore
  8. Cheng-Yu Lee  Is a corresponding author
  1. University of Michigan, United States
  2. Fred Hutchinson Cancer Research Center, United States
  3. National Institute of Genetics, Japan
  4. Stockholm University, Sweden
  5. Riken Brain Science Institute, Japan
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Cite this article as: eLife 2020;9:e56187 doi: 10.7554/eLife.56187

Abstract

Stem cells that indirectly generate differentiated cells through intermediate progenitors drives vertebrate brain evolution. Due to a lack of lineage information, how stem cell functionality, including the competency to generate intermediate progenitors, becomes extinguished during progenitor commitment remains unclear. Type II neuroblasts in fly larval brains divide asymmetrically to generate a neuroblast and a progeny that commits to an intermediate progenitor (INP) identity. We identified Tailless (Tll) as a master regulator of type II neuroblast functional identity, including the competency to generate INPs. Successive expression of transcriptional repressors functions through Hdac3 to silence tll during INP commitment. Reducing repressor activity allows re-activation of Notch in INPs to ectopically induce tll expression driving supernumerary neuroblast formation. Knocking down hdac3 function prevents downregulation of tll during INP commitment. We propose that continual inactivation of stem cell identity genes allows intermediate progenitors to stably commit to generating diverse differentiated cells during indirect neurogenesis.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE152636.

The following data sets were generated

Article and author information

Author details

  1. Noemi Rives- Quinto

    Life Sciences Institute, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Hideyuki Komori

    Center for Stem Cell Biology, Life Sciences Institute, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Cyrina M Ostgaard

    Life Sciences Institute, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Derek H Janssens

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Shu Kondo

    Genetic Strains Research Center, National Institute of Genetics, Mishima, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4625-8379
  6. Qi Dai

    Molecular BioScience, the Winner-Gren Institute, Stockholm University, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  7. Adrian W Moore

    Riken Brain Science Institute, Wako, Japan
    Competing interests
    The authors declare that no competing interests exist.
  8. Cheng-Yu Lee

    Life Sciences Institute, University of Michigan, Ann Arbor, United States
    For correspondence
    leecheng@umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2291-1297

Funding

National Institute of Neurological Disorders and Stroke (R01NS107496)

  • Hideyuki Komori
  • Cheng-Yu Lee

National Institute of Neurological Disorders and Stroke (R01NS111647)

  • Hideyuki Komori
  • Cheng-Yu Lee

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

Reviewing Editor

  1. Claude Desplan, New York University, United States

Publication history

  1. Received: February 20, 2020
  2. Accepted: November 25, 2020
  3. Accepted Manuscript published: November 26, 2020 (version 1)
  4. Version of Record published: December 10, 2020 (version 2)

Copyright

© 2020, Rives- Quinto 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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