Identification of putative enhancer-like elements predicts regulatory networks active in planarian adult stem cells

  1. Jakke Neiro  Is a corresponding author
  2. Divya Sridhar
  3. Anish Dattani
  4. Aziz Aboobaker  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. University of Exeter, United Kingdom

Abstract

Planarians have become an established model system to study regeneration and stem cells, but the regulatory elements in the genome remain almost entirely undescribed. Here, by integrating epigenetic and expression data we use multiple sources of evidence to predict enhancer elements active in the adult stem cell populations that drive regeneration. We have used ChIP-seq data to identify regions with histone modifications consistent with enhancer identity and activity, and ATAC-seq data to identify accessible chromatin. Overlapping these signals allowed for the identification of a set of high confidence candidate enhancers predicted to be active in planarian adult stem cells. These enhancers are enriched for predicted transcription factor (TF) binding sites for TFs and TF families expressed in planarian adult stem cells. Foot-printing analyses provided further evidence that these potential TF binding sites are potentially occupied in adult stem cells. We integrated these analyses to build testable hypotheses for the regulatory function of transcription factors in stem cells, both with respect to how pluripotency might be regulated, and to how lineage differentiation programs are controlled. We found that our predicted GRNs were independently supported by existing TF RNAi/RNA-seq data sets, providing further evidence that our work predicts active enhancers regulating adult stem cells and regenerative mechanisms.

Data availability

Data and analyses are available at https://jakke-neiro.github.io/OxplatysAll analysis code is provided in supplementary fileNew sequence data are available at the NCBI under Bioproject ID PRJNA832235,https://www.ncbi.nlm.nih.gov/bioproject/832235

The following data sets were generated

Article and author information

Author details

  1. Jakke Neiro

    Department of Zoology, University of Oxford, Oxford, United Kingdom
    For correspondence
    jakke.neiro@queens.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  2. Divya Sridhar

    Department of Zoology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Anish Dattani

    Living Systems Institute, University of Exeter, Exeter, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2211-1521
  4. Aziz Aboobaker

    Department of Zoology, University of Oxford, Oxford, United Kingdom
    For correspondence
    aziz.aboobaker@zoo.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4902-5797

Funding

Medical Research Council (MR/T028165/1)

  • Aziz Aboobaker

Biotechnology and Biological Sciences Research Council (BB/J014427/1)

  • Anish Dattani

Biotechnology and Biological Sciences Research Council (BB/M011224/1)

  • Jakke Neiro

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

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Publication history

  1. Received: May 5, 2022
  2. Accepted: August 23, 2022
  3. Accepted Manuscript published: August 23, 2022 (version 1)

Copyright

© 2022, Neiro 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. Jakke Neiro
  2. Divya Sridhar
  3. Anish Dattani
  4. Aziz Aboobaker
(2022)
Identification of putative enhancer-like elements predicts regulatory networks active in planarian adult stem cells
eLife 11:e79675.
https://doi.org/10.7554/eLife.79675

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