Enforcement of developmental lineage specificity by transcription factor Oct1

  1. Zuolian Shen
  2. Jinsuk Kang
  3. Arvind Shakya
  4. Marcin Tabaka
  5. Elke A Jarboe
  6. Aviv Regev
  7. Dean Tantin  Is a corresponding author
  1. Celgene Corporation, United States
  2. The Broad Institute of MIT and Harvard, United States
  3. University of Utah School of Medicine, United States

Abstract

Embryonic stem cells co-express Oct4 and Oct1, a related protein with similar DNA binding specificity. To study the role of Oct1 in ESC pluripotency and transcriptional control, we constructed germline and inducible-conditional Oct1 deficient ESC lines. ESCs lacking Oct1 show normal appearance, self-renewal and growth, but manifest defects upon differentiation. They fail to form beating cardiomyocytes, generate neurons poorly, form small, poorly differentiated teratomas, and cannot generate chimeric mice. Upon RA-mediated differentiation, Oct1 deficient cells induce lineage-appropriate developmentally poised genes poorly while lineage-inappropriate genes, including extra-embryonic genes, are inappropriately expressed. In ESCs Oct1 co-occupies a specific set of targets with Oct4, but does not occupy differentially expressed developmental targets. Instead, Oct1 occupies these targets as cells differentiate and Oct4 declines. These results identify a dynamic interplay between Oct1 and Oct4, in particular during the critical window immediately after loss of pluripotency when cells make the earliest developmental fate decisions.

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The following data sets were generated

Article and author information

Author details

  1. Zuolian Shen

    Celgene Corporation, San Diego, United States
    Competing interests
    No competing interests declared.
  2. Jinsuk Kang

    Celgene Corporation, San Diego, United States
    Competing interests
    No competing interests declared.
  3. Arvind Shakya

    Celgene Corporation, San Diego, United States
    Competing interests
    No competing interests declared.
  4. Marcin Tabaka

    The Broad Institute of MIT and Harvard, Cambridge, United States
    Competing interests
    No competing interests declared.
  5. Elke A Jarboe

    Department of Pathology, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  6. Aviv Regev

    The Broad Institute of MIT and Harvard, Cambridge, United States
    Competing interests
    Aviv Regev, Senior editor, eLife.
  7. Dean Tantin

    Department of Pathology, University of Utah School of Medicine, Salt Lake City, United States
    For correspondence
    dean.tantin@path.utah.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1354-8385

Funding

National Institute of Allergy and Infectious Diseases (R01AI100873)

  • Dean Tantin

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 (#14-06015) of the University of Utah. Every effort was made to minimize suffering.

Reviewing Editor

  1. Clare Blackburn, MRC Centre for Regenerative Medicine, University of Edinburgh, United Kingdom

Publication history

  1. Received: August 25, 2016
  2. Accepted: May 23, 2017
  3. Accepted Manuscript published: May 24, 2017 (version 1)
  4. Version of Record published: June 9, 2017 (version 2)

Copyright

© 2017, Shen 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. Zuolian Shen
  2. Jinsuk Kang
  3. Arvind Shakya
  4. Marcin Tabaka
  5. Elke A Jarboe
  6. Aviv Regev
  7. Dean Tantin
(2017)
Enforcement of developmental lineage specificity by transcription factor Oct1
eLife 6:e20937.
https://doi.org/10.7554/eLife.20937
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